Toxins

Research

659 KiB

Open AccessArticle

Wavelength-Dependent Degradation of Ochratoxin and Citrinin by Light in Vitro and in Vivo and Its Implications on Penicillium

by Markus Schmidt-Heydt, Benedikt Cramer, Irina Graf, Sandra Lerch, Hans-Ulrich Humpf and Rolf Geisen

Toxins 2012, 4(12), 1535-1551; https://doi.org/10.3390/toxins4121535 - 14 Dec 2012

Cited by 41 | Viewed by 9413

Abstract

It has previously been shown that the biosynthesis of the mycotoxins ochratoxin A and B and of citrinin by Penicillium is regulated by light. However, not only the biosynthesis of these mycotoxins, but also the molecules themselves are strongly affected by light of [...] Read more.

It has previously been shown that the biosynthesis of the mycotoxins ochratoxin A and B and of citrinin by Penicillium is regulated by light. However, not only the biosynthesis of these mycotoxins, but also the molecules themselves are strongly affected by light of certain wavelengths. The white light and blue light of 470 and 455 nm are especially able to degrade ochratoxin A, ochratoxin B and citrinin after exposure for a certain time. After the same treatment of the secondary metabolites with red (627 nm), yellow (590 nm) or green (530 nm) light or in the dark, almost no degradation occurred during that time indicating the blue light as the responsible part of the spectrum. The two derivatives of ochratoxin (A and B) are degraded to certain definitive degradation products which were characterized by HPLC-FLD-FTMS. The degradation products of ochratoxin A and B did no longer contain phenylalanine however were still chlorinated in the case of ochratoxin A. Citrinin is completely degraded by blue light. A fluorescent band was no longer visible after detection by TLC suggesting a higher sensitivity and apparently greater absorbance of energy by citrinin. The fact that especially blue light degrades the three secondary metabolites is apparently attributed to the absorption spectra of the metabolites which all have an optimum in the short wave length range. The absorption range of citrinin is, in particular, broader and includes the wave length of blue light. In wheat, which was contaminated with an ochratoxin A producing culture of Penicillium verrucosum and treated with blue light after a pre-incubation by the fungus, the concentration of the preformed ochratoxin A reduced by roughly 50% compared to the control and differed by > 90% compared to the sample incubated further in the dark. This indicates that the light degrading effect is also exerted in vivo, e.g., on food surfaces. The biological consequences of the light instability of the toxins are discussed. Full article

(This article belongs to the Special Issue Ochratoxins)

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189 KiB

Open AccessArticle

Ochratoxin A Contamination of Food from Croatia

by Maja Peraica, Dubravka Flajs, Ana-Marija Domijan, Dario Ivić and Bogdan Cvjetković

Toxins 2010, 2(8), 2098-2105; https://doi.org/10.3390/toxins2082098 - 10 Aug 2010

Cited by 15 | Viewed by 10136

Abstract

Ochratoxin A (OTA) is a mycotoxin with nephrotoxic, genotoxic and carcinogenic properties produced by Penicillium and Aspergillus moulds under different climatic conditions. Humans and animals are exposed to this compound mainly via ingestion of contaminated food. In Croatia, research on mycotoxins focused on [...] Read more.

Ochratoxin A (OTA) is a mycotoxin with nephrotoxic, genotoxic and carcinogenic properties produced by Penicillium and Aspergillus moulds under different climatic conditions. Humans and animals are exposed to this compound mainly via ingestion of contaminated food. In Croatia, research on mycotoxins focused on OTA when the mycotoxin theory of endemic nephropathy (EN) was postulated. Ochratoxin A was more frequent and at higher concentration in foods from EN than those from the control regions. Subsequently, OTA concentrations were determined in some commodities intended for human consumption such as maize, wheat, beans and wine. Samples from all parts of Croatia were analyzed and OTA was found in all types of commodities. It was frequently found together with other mycotoxins (fumonisin B₁, fumonisin B₂ and zearalenone). In general, OTA concentration in foods from Croatia is low, but the frequency of positive samples shows considerable variations from year to year depending also on sampling location. Although low levels of OTA were found in a large proportion of analyzed food samples, its persistent co-occurrence with other significant mycotoxins should raise serious public health concerns as there interactions may be synergistic or additive in causing toxicity in humans and animals. There is need to establish control measures through which such contaminations in foods can be managed. Full article

(This article belongs to the Special Issue Ochratoxins)

199 KiB

Open AccessArticle

Natural Occurrence of Ochratoxin A in Musts, Wines and Grape Vine Fruits from Grapes Harvested in Argentina

by María Lorena Ponsone, María Laura Chiotta, Mariana Combina, Adriana Torres, Patricia Knass, Ana Dalcero and Sofía Chulze

Toxins 2010, 2(8), 1984-1996; https://doi.org/10.3390/toxins2081984 - 3 Aug 2010

Cited by 23 | Viewed by 9798

Abstract

In this study, ochratoxin A (OTA) occurrence in Argentinean musts, wines and dried vine fruits was evaluated, alongside with the performance of OchraStar^TM columns for OTA extraction. In all the three matrices analyzed, the OchraStar^TMcolumns showed good performance. The analysis [...] Read more.

In this study, ochratoxin A (OTA) occurrence in Argentinean musts, wines and dried vine fruits was evaluated, alongside with the performance of OchraStar^TM columns for OTA extraction. In all the three matrices analyzed, the OchraStar^TMcolumns showed good performance. The analysis of natural occurrence of OTA in the red must and the red wine samples showed low incidence with low levels of mean OTA contamination (0.12 ng/mL and 0.37 ng/mL, respectively), while 60% of the dried vine fruit samples were contaminated with OTA, in levels ranging from 0.26 to 20.28 ng/g. Full article

(This article belongs to the Special Issue Ochratoxins)

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239 KiB

Open AccessArticle

Development and Characterization of a Monoclonal Antibody against Ochratoxin B and Its Application in ELISA

by Alexandra H. Heussner, Simon Ausländer and Daniel R. Dietrich

Toxins 2010, 2(6), 1582-1594; https://doi.org/10.3390/toxins2061582 - 21 Jun 2010

Cited by 13 | Viewed by 9102

Abstract

A monoclonal antibody specific to ochratoxin B (OTB) was employed for the development of an indirect competitive OTB-ELISA. The optimized OTB-ELISA resulted in a limit of detection (LOD) for OTB of 3 µg/L (8 nM), a limit of quantification (LOQ) of 3.7 µg/L [...] Read more.

A monoclonal antibody specific to ochratoxin B (OTB) was employed for the development of an indirect competitive OTB-ELISA. The optimized OTB-ELISA resulted in a limit of detection (LOD) for OTB of 3 µg/L (8 nM), a limit of quantification (LOQ) of 3.7 µg/L (10 nM), and a 50% inhibitory concentration (IC50) of 150 nM. Due to very low cross-reactivity to OTA (2.7%) and structurally related molecules (0%), this OTB-ELISA was found to be suitable to detect OTB with excellent precision in different matrices, i.e., beer, coffee and wine. Therefore, this OTB-ELISA will allow screening of OTB in food and feed products. Full article

(This article belongs to the Special Issue Ochratoxins)

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433 KiB

Open AccessArticle

Ochratoxin A: In Utero Exposure in Mice Induces Adducts in Testicular DNA

by Jamie E. Jennings-Gee, Mariana Tozlovanu, Richard Manderville, Mark Steven Miller, Annie Pfohl-Leszkowicz and Gary G. Schwartz

Toxins 2010, 2(6), 1428-1444; https://doi.org/10.3390/toxins2061428 - 11 Jun 2010

Cited by 51 | Viewed by 11360

Abstract

Ochratoxin A (OTA) is a nephrotoxin and carcinogen that is associated with Balkan endemic nephropathy and urinary tract tumors. OTA crosses the placenta and causes adducts in the liver and kidney DNA of newborns. Because the testis and kidney develop from the same [...] Read more.

Ochratoxin A (OTA) is a nephrotoxin and carcinogen that is associated with Balkan endemic nephropathy and urinary tract tumors. OTA crosses the placenta and causes adducts in the liver and kidney DNA of newborns. Because the testis and kidney develop from the same embryonic tissue, we reasoned that OTA also may cause adducts transplacentally in the testis. We tested the hypothesis that acute exposure to OTA, via food and via exposure in utero, causes adducts in testicular DNA and that these lesions are identical to those that can be produced in the kidney and testis by the consumption of OTA. Adult mice received a single dose of OTA (from 0–1,056 µg/kg) by gavage. Pregnant mice received a single i.p. injection of OTA (2.5 mg/kg) at gestation day 17. DNA adducts were determined by ³²P-postlabeling. Gavage-fed animals sacrificed after 48 hours accumulated OTA in kidney and testis and showed DNA adducts in kidney and testis. Some OTA metabolites isolated from the tissues were similar in both organs (kidney and testis). The litters of mice exposed prenatally to OTA showed no signs of overt toxicity. However, newborn and 1-month old males had DNA adducts in kidney and testis that were chromatographically similar to DNA adducts observed in the kidney and testis of gavage-fed adults. One adduct was identified previously as C8-dG-OTA adduct by LC MS/MS. No adducts were observed in males from dams not exposed to OTA. Our findings that in utero exposure to OTA causes adducts in the testicular DNA of male offspring support a possible role for OTA in testicular cancer. Full article

(This article belongs to the Special Issue Ochratoxins)

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2349 KiB

Open AccessArticle

Differential Cell Sensitivity between OTA and LPS upon Releasing TNF-α

by Lauy Al-Anati, Ebtisam Essid, Ulla Stenius, Knut Beuerlein, Klaus Schuh and Ernst Petzinger

Toxins 2010, 2(6), 1279-1299; https://doi.org/10.3390/toxins2061279 - 1 Jun 2010

Cited by 14 | Viewed by 11709

Abstract

The release of tumor necrosis factor α (TNF-α) by ochratoxin A (OTA) was studied in various macrophage and non-macrophage cell lines and compared with E. coli lipopolysaccharide (LPS) as a standard TNF-α release agent. Cells were exposed either to 0, 2.5 or 12.5 [...] Read more.

The release of tumor necrosis factor α (TNF-α) by ochratoxin A (OTA) was studied in various macrophage and non-macrophage cell lines and compared with E. coli lipopolysaccharide (LPS) as a standard TNF-α release agent. Cells were exposed either to 0, 2.5 or 12.5 µmol/L OTA, or to 0.1 µg/mL LPS, for up to 24 h. OTA at 2.5 µmol/L and LPS at 0.1 µg/mL were not toxic to the tested cells as indicated by viability markers. TNF-a was detected in the incubated cell medium of rat Kupffer cells, peritoneal rat macrophages, and the mouse monocyte macrophage cell line J774A.1: TNF-a concentrations were 1,000 pg/mL, 1,560 pg/mL, and 650 pg/mL, respectively, for 2.5 µmol/L OTA exposure and 3,000 pg/mL, 2,600 pg/mL, and 2,115 pg/mL, respectively, for LPS exposure. Rat liver sinusoidal endothelial cells, rat hepatocytes, human HepG2 cells, and mouse L929 cells lacked any cytokine response to OTA, but showed a significant release of TNF-a after LPS exposure, with the exception of HepG2 cells. In non-responsive cell lines, OTA lacked both any activation of NF-κB or the translocation of activated NF-κB to the cell nucleus, i.e., in mouse L929 cells. In J774A.1 cells, OTA mediated TNF-a release via the pRaf/MEK 1/2–NF-κB and p38-NF-κB pathways, whereas LPS used pRaf/MEK 1/2-NF-κB, but not p38-NF-κB pathways. In contrast, in L929 cells, LPS used other pathways to activate NF-κB. Our data indicate that only macrophages and macrophage derived cells respond to OTA and are considered as sources for TNF-a release upon OTA exposure. Full article

(This article belongs to the Special Issue Ochratoxins)

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273 KiB

Open AccessArticle

Alpha-Tocopherol Counteracts the Cytotoxicity Induced by Ochratoxin A in Primary Porcine Fibroblasts

by Eleonora Fusi, Raffaella Rebucci, Chiara Pecorini, Anna Campagnoli, Luciano Pinotti, Francesca Saccone, Federica Cheli, Stig Purup, Kristen Sejrsen and Antonella Baldi

Toxins 2010, 2(6), 1265-1278; https://doi.org/10.3390/toxins2061265 - 1 Jun 2010

Cited by 30 | Viewed by 10959

Abstract

The aims of the current study were to determine the half-lethal concentration of ochratoxin A (OTA) as well as the levels of lactate dehydrogenase release and DNA fragmentation induced by OTA in primary porcine fibroblasts, and to examine the role of α-tocopherol in [...] Read more.

The aims of the current study were to determine the half-lethal concentration of ochratoxin A (OTA) as well as the levels of lactate dehydrogenase release and DNA fragmentation induced by OTA in primary porcine fibroblasts, and to examine the role of α-tocopherol in counteracting its toxicity. Cells showed a dose-, time- and origin-dependent (ear vs. embryo) sensitivity to ochratoxin A. Pre-incubation for 3 h with 1 nM α-tocopherol significantly (P < 0.01) reduced OTA cytotoxicity, lactate dehydrogenase release and DNA damage in both fibroblast cultures. These findings indicate that α-tocopherol supplementation may counteract short-term OTA toxicity, supporting its defensive role in the cell membrane. Full article

(This article belongs to the Special Issue Ochratoxins)

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480 KiB

Open AccessArticle

Pathological Outcomes in Kidney and Brain in Male Fischer Rats Given Dietary Ochratoxin A, Commencing at One Year of Age

by Peter G. Mantle and Christopher C. Nolan

Toxins 2010, 2(5), 1100-1110; https://doi.org/10.3390/toxins2051100 - 13 May 2010

Cited by 19 | Viewed by 11504

Abstract

Malignant renal carcinoma, manifest in morbid ageing rats, is the striking component of an otherwise silent response after about nine months of exposure to ochratoxin A in the first year of life (daily intake ~100–250 µg/kg body weight). Reasons for the long latency [...] Read more.

Malignant renal carcinoma, manifest in morbid ageing rats, is the striking component of an otherwise silent response after about nine months of exposure to ochratoxin A in the first year of life (daily intake ~100–250 µg/kg body weight). Reasons for the long latency are unclear, as is whether there would be a similar carcinogenic response if toxin exposure started at one year of age. Therefore, 24 male Fischer rats were given 100 µg ochratoxin A as a daily dietary contaminant for 35 weeks from age 50 weeks. Plasma ochratoxin A concentration reached a maximum value of ~8 µg/mL within one month of starting the toxin regimen. No renal carcinomas occurred. Four renal adenomas, two of which were only microscopic, were found among the six rats surviving for 110 weeks. The findings raise new questions about a difference between young adults and mature adults in sensitivity of male rats to the ochratoxin A-induced DNA damage necessary for renal carcinogenesis. A pilot histological study of perfuse-fixed brains of the toxin-treated rats showed no gross abnormalities, correlating with the consistent absence of behavioral or neurological disorders from chronic ochratoxin A exposure regimens in the range 100–250 µg/kg/day during the second half of life. Reasoned questioning concerning ochratoxin A as a neurotoxic mycotoxin is made. Full article

(This article belongs to the Special Issue Ochratoxins)

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339 KiB

Open AccessArticle

Occurrence of Ochratoxin A in Southern Spanish Generous Wines under the Denomination of Origin “Jerez-Xérès-Sherry and ‘Manzanilla’ Sanlúcar de Barrameda”

by Mª Teresa Murillo-Arbizu, Susana Amézqueta, Elena González-Peñas and Adela López De Cerain

Toxins 2010, 2(5), 1054-1064; https://doi.org/10.3390/toxins2051054 - 12 May 2010

Cited by 14 | Viewed by 10044

Abstract

The mycotoxin ochratoxin A (OTA) has toxic effects in animals; the most relevant of them is nephrotoxicity. OTA has also been classified as a possible carcinogen for humans (group 2B) by the International Agency for Research on Cancer (IARC). Therefore, exposure to OTA [...] Read more.

The mycotoxin ochratoxin A (OTA) has toxic effects in animals; the most relevant of them is nephrotoxicity. OTA has also been classified as a possible carcinogen for humans (group 2B) by the International Agency for Research on Cancer (IARC). Therefore, exposure to OTA through contaminated food can represent health impairment to humans. The maximum permitted level for this mycotoxin in wine is 2.0 mg/L. The presence of OTA in Spanish wines produced using the traditional methods under the Denomination of Origin “Jerez-Xérès-Sherry and manzanilla Sanlúcar de Barrameda” was evaluated by a High performance Liquid Chromatography method with fluorescence detection and immunoaffinity column purification. A recovery of 95.4% and a limit of detection and quantification of 0.009 mg/L and 0.02 mg/L respectively, were achieved. In manzanilla, fino, amontillado and oloroso wine, the mean OTA values were 0.042, 0.044, 0.144, and 0.319 mg/L, respectively. These levels are not different from other data given in the reference literature on white wines, although fino and manzanilla wines have very low OTA levels. Full article

(This article belongs to the Special Issue Ochratoxins)

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373 KiB

Open AccessArticle

Occurrence of Black Aspergilli and Ochratoxin A on Grapes in Italy

by Gianluca Lucchetta, Irene Bazzo, Gianluca Dal Cortivo, Lisa Stringher, Diego Bellotto, Michele Borgo and Elisa Angelini

Toxins 2010, 2(4), 840-855; https://doi.org/10.3390/toxins2040840 - 21 Apr 2010

Cited by 33 | Viewed by 10102

Abstract

Ochratoxin A (OTA) in wine is linked to contamination by several Aspergillus species. In 2003–2007, grape samples collected in Italy were surveyed for the presence of OTA and OTA-producing fungi. A. niger aggregate was the prevalent species. A. carbonarius, which is considered [...] Read more.

Ochratoxin A (OTA) in wine is linked to contamination by several Aspergillus species. In 2003–2007, grape samples collected in Italy were surveyed for the presence of OTA and OTA-producing fungi. A. niger aggregate was the prevalent species. A. carbonarius, which is considered the main source of OTA in grapes, was mostly found in Southern Italy. The year and the environment had an important influence on the development of the black Aspergillus populations. Testing with ELISA showed OTA to be present in about 30% of the samples. Samples from Southern Italy showed the highest occurrence (45%) and also the highest OTA concentration, sometimes higher than 2 mg/L. The values decreased progressively the further North the samples were taken. Full article

(This article belongs to the Special Issue Ochratoxins)

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166 KiB

Open AccessArticle

Ochratoxin A and β2-Microglobulin in BEN Patients and Controls

by Pavlina Yordanova, Karmaus Wilfried, Svetla Tsolova and Plamen Dimitrov

Toxins 2010, 2(4), 780-792; https://doi.org/10.3390/toxins2040780 - 20 Apr 2010

Cited by 10 | Viewed by 9968

Abstract

Ochratoxin A (OTA) is a mycotoxin naturally occurring in different foods. OTA is arguably a risk factor for Balkan endemic nephropathy (BEN). The aims of this study are to (1) test the OTA-BEN association in BEN-groups and controls and (2) determine whether urine [...] Read more.

Ochratoxin A (OTA) is a mycotoxin naturally occurring in different foods. OTA is arguably a risk factor for Balkan endemic nephropathy (BEN). The aims of this study are to (1) test the OTA-BEN association in BEN-groups and controls and (2) determine whether urine β2-microglobulin, a marker of impaired ability of the kidneys to re-absorb, is related to OTA. BEN patients had significantly higher OTA serum levels. Within the offspring, OTA was significantly related to higher β2-microglobulin excretion. OTA (2005/2006) was related to a higher incidence of BEN after 2008, providing further evidence that OTA is a risk factor for BEN. Full article

(This article belongs to the Special Issue Ochratoxins)

226 KiB

Open AccessArticle

Ochratoxin A and Aflatoxins in Liquorice Products

by Amedeo Pietri, Silvia Rastelli and Terenzio Bertuzzi

Toxins 2010, 2(4), 758-770; https://doi.org/10.3390/toxins2040758 - 20 Apr 2010

Cited by 30 | Viewed by 10023

Abstract

The occurrence of ochratoxin A (OTA) and aflatoxins (AFs) in liquorice products made in Italy was surveyed. Twenty-eight samples of dried liquorice extract and fifty-four of liquorice confectionery (liquorice content between 2 and 10%) were collected from retail outlets located in northern Italy. [...] Read more.

The occurrence of ochratoxin A (OTA) and aflatoxins (AFs) in liquorice products made in Italy was surveyed. Twenty-eight samples of dried liquorice extract and fifty-four of liquorice confectionery (liquorice content between 2 and 10%) were collected from retail outlets located in northern Italy. After extraction and purification through an immunoaffinity column, OTA and AFs were analysed using both HPLC-FLD and HPLC-MS/MS. OTA occurred in all samples of dried liquorice extract and in 61% of samples of liquorice confectionery, showing very high values for the former (mean 89.6 µg kg^-1, maximum value 990.1 µg kg^-1), and relatively low levels for the latter (mean 0.96 µg kg^-1, maximum value 8.3 µg kg^-1). The contribution of dried liquorice extract to OTA intake appears to be non-negligible for children, who are potentially high consumers. AF contamination resulted very low: AFB₁ was detected only in 15.8% of samples (maximum value 7.7 µg kg^-1, mean 0.38 and 0.41 µg kg^-1 for dried liquorice extract and liquorice confectionery, respectively); the other AFs were not detected. To our knowledge, it is the first time that AFB₁ has been detected in liquorice extract samples. Full article

(This article belongs to the Special Issue Ochratoxins)

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Open AccessArticle

Studies on Carcinogenic and Toxic Effects of Ochratoxin A in Chicks

by Stoycho D. Stoev

Toxins 2010, 2(4), 649-664; https://doi.org/10.3390/toxins2040649 - 12 Apr 2010

Cited by 69 | Viewed by 11863

Abstract

Carcinogenic/toxic effects of ochratoxin A (OTA) in various internal organs of Plymouth Rock chicks were determined. The number of OTA-induced neoplasms was similar in chicks given 25 ppm L-β-phenylalanine (PHE) in addition to 5 ppm OTA compared to chicks given only 5 ppm [...] Read more.

Carcinogenic/toxic effects of ochratoxin A (OTA) in various internal organs of Plymouth Rock chicks were determined. The number of OTA-induced neoplasms was similar in chicks given 25 ppm L-β-phenylalanine (PHE) in addition to 5 ppm OTA compared to chicks given only 5 ppm OTA, which showed that PHE cannot be used as a real protector against the carcinogenic or toxic effects of OTA in chicks. OTA was found to provoke strong degenerative changes in liver and kidneys, degenerative changes and depletion of cells in lymphoid organs, oedematous and degenerative changes in the brain, muscular haemorrhages and fatty changes in the bone marrow. The target organs for carcinogenic effect of OTA in chicks were found to be kidneys and liver. Full article

(This article belongs to the Special Issue Ochratoxins)

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1277 KiB

Open AccessArticle

Oncological Outcomes in Rats Given Nephrocarcinogenic Exposure to Dietary Ochratoxin A, Followed by the Tumour Promoter Sodium Barbital for Life: A Pilot Study

by Peter G. Mantle, Miloslav Dobrota, Cheryl E. Gillett, Edward W. Odell and Sarah E. Pinder

Toxins 2010, 2(4), 552-571; https://doi.org/10.3390/toxins2040552 - 31 Mar 2010

Cited by 9 | Viewed by 9680

Abstract

The potent experimental renal carcinogenesis of ochratoxin A (OTA) in male rats makes the dietary contaminant a potential factor in human oncology. We explored whether the tumour promoter sodium barbitate could shorten the otherwise long latency between exposure to toxin and tumourigenesis. Young [...] Read more.

The potent experimental renal carcinogenesis of ochratoxin A (OTA) in male rats makes the dietary contaminant a potential factor in human oncology. We explored whether the tumour promoter sodium barbitate could shorten the otherwise long latency between exposure to toxin and tumourigenesis. Young rats, of a hybrid in which mononuclear leukaemia was rare, were given feed contaminated (5 ppm) with OTA for 36 weeks to initiate renal tumourigenesis. Some individuals were thereafter given sodium barbitate (500 ppm in drinking water) for life. Pathological outcomes were studied at or near the end of natural life. Renal tumours in males given barbitate became evident after latency of one year, but only slightly before those without barbitate. In contrast, female mammary tumourigenesis was advanced by at least 6 months synchronously in all rats given the OTA-barbitate regimen compared to tumourigenesis in controls. Diagnosis of malignant mammary angiosarcoma in a female given the OTA-barbitate regimen is a new finding in the rat. The long latency of OTA-induced renal tumourigenesis was not notably susceptible to accelerated promotion by barbitate, contrasting with an apparently marked effect of barbitate on development of mammary tumours. Full article

(This article belongs to the Special Issue Ochratoxins)

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Open AccessArticle

A Pilot Study of Nuclear Instability in Archived Renal and Upper Urinary Tract Tumours with Putative Ochratoxin Aetiology

by Peter G. Mantle, Cyrille Amerasinghe, Amy L. Brown, Diana Herman, Thomas Horn, Thoger Krogh, Edward W. Odell, Tomas Rosenbaum and Calin A. Tatu

Toxins 2010, 2(3), 326-340; https://doi.org/10.3390/toxins2030326 - 9 Mar 2010

Cited by 4 | Viewed by 11268

Abstract

DNA ploidy measurement has been applied uniquely to wax-embedded tissue of primary renal cell and metastatic tumours of a key experimental researcher on porcine ochratoxicosis, a control, and four transitional cell carcinomas from cases of Balkan endemic nephropathy. Primary renal tumour was diploid, [...] Read more.

DNA ploidy measurement has been applied uniquely to wax-embedded tissue of primary renal cell and metastatic tumours of a key experimental researcher on porcine ochratoxicosis, a control, and four transitional cell carcinomas from cases of Balkan endemic nephropathy. Primary renal tumour was diploid, and hyperdiploid metastasis was within the lower ploidy range for typical renal cell carcinoma. Three Balkan primary tumours showed extensive aneuploidy indicating marked nuclear instability, similar to model rat renal carcinoma caused by ochratoxin A. In contrast, much less nuclear instability in the putative occupational ochratoxicosis case fitted poorly with the ochratoxin A model. Full article

(This article belongs to the Special Issue Ochratoxins)

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Review

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142 KiB

Open AccessReview

Ecophysiology of Aspergillus Section Nigri Species Potential Ochratoxin A Producers

by Andrea L. Astoreca, Carina E. Magnoli and Ana M. Dalcero

Toxins 2010, 2(11), 2593-2605; https://doi.org/10.3390/toxins2112593 - 29 Oct 2010

Cited by 28 | Viewed by 8975

Abstract

After aflatoxins, ochratoxin A (OTA) is the most studied mycotoxin due to the toxicological significance in human and animal diets. OTA presence has been extensively reported worldwide in the last decade in several agricultural products. The main OTA producer in tropical and temperate [...] Read more.

After aflatoxins, ochratoxin A (OTA) is the most studied mycotoxin due to the toxicological significance in human and animal diets. OTA presence has been extensively reported worldwide in the last decade in several agricultural products. The main OTA producer in tropical and temperate climates is Aspergillus carbonarius followed by species belonging to A. niger aggregate. Currently, many scientists worldwide have studied the influence of water activity and temperature for growth and biosynthesis of OTA by these species on synthetic media. This article reviews ecophysiological studies of Aspergillus section Nigri strains on synthetic media and natural substrates. The results of these investigations suggest that significant amounts of OTA can be produced in only five days and that the use of different storage practices, such as a_W and temperature levels below 0.930 and 15 °C, respectively, allow controlling fungal contamination and minimizing the OTA production in several products as peanuts, corn, dried grapes and derived products for human consumption. Full article

(This article belongs to the Special Issue Ochratoxins)

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Open AccessReview

Rapid Visual Tests: Fast and Reliable Detection of Ochratoxin A

by Ingrid Bazin, Elodie Nabais and Miguel Lopez-Ferber

Toxins 2010, 2(9), 2230-2241; https://doi.org/10.3390/toxins2092230 - 26 Aug 2010

Cited by 45 | Viewed by 13289

Abstract

This paper reviews the early detection strategies that have been employed for the rapid monitoring of ochratoxin A (OTA) contamination of food. OTA, a mycotoxin mainly produced by some Aspergillus and Penicillium species, is found in cereals, coffee, wine, pork and grapes. To [...] Read more.

This paper reviews the early detection strategies that have been employed for the rapid monitoring of ochratoxin A (OTA) contamination of food. OTA, a mycotoxin mainly produced by some Aspergillus and Penicillium species, is found in cereals, coffee, wine, pork and grapes. To minimize the entry of this mycotoxin into the food chain, rapid diagnostic tools are required. To this end, the potential use of lateral flow devices has also been developed. In this study, we analyze the robustness of test strips using published methods for colorimetric detection. Different test formats are discussed, and challenges in the development of lateral flow devices for on-site determination of OTA, with requirements such as robustness, speed, and cost-effectiveness, are discussed. Full article

(This article belongs to the Special Issue Ochratoxins)

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Open AccessReview

Effects of Ochratoxin A on Livestock Production

by Gianni Battacone, Anna Nudda and Giuseppe Pulina

Toxins 2010, 2(7), 1796-1824; https://doi.org/10.3390/toxins2071796 - 8 Jul 2010

Cited by 79 | Viewed by 12657

Abstract

Ochratoxin A (OTA) contamination often causes large economic losses on livestock production. The intake of feed contaminated by OTA also represents a potential risk for animal health and a food safety issue due to the transfer of the toxin through the food chain [...] Read more.

Ochratoxin A (OTA) contamination often causes large economic losses on livestock production. The intake of feed contaminated by OTA also represents a potential risk for animal health and a food safety issue due to the transfer of the toxin through the food chain to humans. The aim of this paper is to review the available literature on: (1) the frequency and degree of occurrence of OTA in different feedstuffs; (2) the toxicological effects of OTA intake on the performance of the main livestock (i.e., poultry, swine, cattle, goats and sheep); and (3) the transfer of OTA, or its metabolites, from animal feed into animal products such as milk, meat and eggs. Full article

(This article belongs to the Special Issue Ochratoxins)

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Open AccessReview

Chemical, Physical and Biological Approaches to Prevent Ochratoxin Induced Toxicoses in Humans and Animals

by János Varga, Sándor Kocsubé, Zsanett Péteri, Csaba Vágvölgyi and Beáta Tóth

Toxins 2010, 2(7), 1718-1750; https://doi.org/10.3390/toxins2071718 - 1 Jul 2010

Cited by 95 | Viewed by 14044

Abstract

Ochratoxins are polyketide derived fungal secondary metabolites with nephrotoxic, immunosuppressive, teratogenic, and carcinogenic properties. Ochratoxin-producing fungi may contaminate agricultural products in the field (preharvest spoilage), during storage (postharvest spoilage), or during processing. Ochratoxin contamination of foods and feeds poses a serious health hazard [...] Read more.

Ochratoxins are polyketide derived fungal secondary metabolites with nephrotoxic, immunosuppressive, teratogenic, and carcinogenic properties. Ochratoxin-producing fungi may contaminate agricultural products in the field (preharvest spoilage), during storage (postharvest spoilage), or during processing. Ochratoxin contamination of foods and feeds poses a serious health hazard to animals and humans. Several strategies have been investigated for lowering the ochratoxin content in agricultural products. These strategies can be classified into three main categories: prevention of ochratoxin contamination, decontamination or detoxification of foods contaminated with ochratoxins, and inhibition of the absorption of consumed ochratoxins in the gastrointestinal tract. This paper gives an overview of the strategies that are promising with regard to lowering the ochratoxin burden of animals and humans. Full article

(This article belongs to the Special Issue Ochratoxins)

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Open AccessReview

Molecularly Imprinted Polymers for Ochratoxin A Extraction and Analysis

by Jorn C. C. Yu and Edward P. C. Lai

Toxins 2010, 2(6), 1536-1553; https://doi.org/10.3390/toxins2061536 - 18 Jun 2010

Cited by 53 | Viewed by 10770

Abstract

Molecularly imprinted polymers (MIPs) are considered as polymeric materials that mimic the functionality of antibodies. MIPs have been utilized for a wide variety of applications in chromatography, solid phase extraction, immunoassays, and sensor recognition. In this article, recent advances of MIPs for the [...] Read more.

Molecularly imprinted polymers (MIPs) are considered as polymeric materials that mimic the functionality of antibodies. MIPs have been utilized for a wide variety of applications in chromatography, solid phase extraction, immunoassays, and sensor recognition. In this article, recent advances of MIPs for the extraction and analysis of ochratoxins are discussed. Selection of functional monomers to bind ochratoxin A (OTA) with high affinities, optimization of extraction procedures, and limitations of MIPs are compared from different reports. The most relevant examples in the literature are described to clearly show how useful these materials are. Strategies on MIP preparation and schemes of analytical methods are also reviewed in order to suggest the next step that would make better use of MIPs in the field of ochratoxin research. The review ends by outlining the remaining issues and impediments. Full article

(This article belongs to the Special Issue Ochratoxins)

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Open AccessReview

«Suspects» in Etiology of Endemic Nephropathy: Aristolochic Acid versus Mycotoxins

by Stjepan Pepeljnjak and Maja Šegvić Klarić

Toxins 2010, 2(6), 1414-1427; https://doi.org/10.3390/toxins2061414 - 11 Jun 2010

Cited by 19 | Viewed by 9138

Abstract

Despite many hypotheses that have been challenged, the etiology of endemic nephropathy (EN) is still unknown. At present, the implications of aristolochic acid (AA) and mycotoxins (ochratoxin A—OTA and citrinin—CIT) are under debate. AA-theory is based on renal pathohistological similarities between Chinese herbs [...] Read more.

Despite many hypotheses that have been challenged, the etiology of endemic nephropathy (EN) is still unknown. At present, the implications of aristolochic acid (AA) and mycotoxins (ochratoxin A—OTA and citrinin—CIT) are under debate. AA-theory is based on renal pathohistological similarities between Chinese herbs nephropathy (CHN) and EN, findings of AA-DNA adducts in EN and in patients with urinary tract tumors (UTT), as well as the domination of A:T→T:A transversions in the p53 mutational spectrum of UTT patients, which corresponds with findings of such mutations in AA-treated rats. However, exposure pathways of EN residents to AA are unclear. Experimental studies attempting to deduce whether nephrotoxins OTA and CIT appear at higher frequencies or levels (or both) in the food and blood or urine of EN residents support the mycotoxin theory. Also, some molecular studies revealed the presence of OTA-DNA adducts in the renal tissue of EN and UTT patients. In this review, data supporting or arguing against AA and mycotoxin theory are presented and discussed. Full article

(This article belongs to the Special Issue Ochratoxins)

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Open AccessReview

Molecular Mechanism of Ochratoxin A Transport in the Kidney

by Naohiko Anzai, Promsuk Jutabha and Hitoshi Endou

Toxins 2010, 2(6), 1381-1398; https://doi.org/10.3390/toxins2061381 - 9 Jun 2010

Cited by 62 | Viewed by 12698

Abstract

The mycotoxin, ochratoxin A (OTA), is thought to be responsible for Balkan endemic nephropathy. OTA accumulates in several tissues, especially in the kidneys and liver. The excretion of OTA into urine is thought to be mainly by tubular secretion, presumably via the organic [...] Read more.

The mycotoxin, ochratoxin A (OTA), is thought to be responsible for Balkan endemic nephropathy. OTA accumulates in several tissues, especially in the kidneys and liver. The excretion of OTA into urine is thought to be mainly by tubular secretion, presumably via the organic anion transport system. Recently, several families of multispecific organic anion transporters have been identified: organic anion transporters (OATs), organic anion-transporting polypeptides (OATPs), oligopeptide transporters (PEPTs), and ATP-binding cassette (ABC) transporters, such as MRP2 and BCRP. These renal transporters mediate the transmembrane transport of OTA and play a pivotal role in the development of OTA-induced nephrotoxicity. Full article

(This article belongs to the Special Issue Ochratoxins)

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Open AccessReview

Ochratoxin A in Portugal: A Review to Assess Human Exposure

by Sofia C. Duarte, Angelina Pena and Celeste M. Lino

Toxins 2010, 2(6), 1225-1249; https://doi.org/10.3390/toxins2061225 - 1 Jun 2010

Cited by 31 | Viewed by 10747

Abstract

In Portugal, the climate, dietary habits, and food contamination levels present the characteristics for higher population susceptibility to ochratoxin A (OTA), one of the known mycotoxins with the greatest public health and agro-economic importance. In this review, following a brief historical insight on [...] Read more.

In Portugal, the climate, dietary habits, and food contamination levels present the characteristics for higher population susceptibility to ochratoxin A (OTA), one of the known mycotoxins with the greatest public health and agro-economic importance. In this review, following a brief historical insight on OTA research, a summary of the available data on OTA occurrence in food (cereals, bread, wine, meat) and biological fluids (blood, urine) is made. With this data, an estimation of intake is made to ascertain and update the risk exposure estimation of the Portuguese population, in comparison to previous studies and other populations. Full article

(This article belongs to the Special Issue Ochratoxins)

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Open AccessReview

Ochratoxin A in Moroccan Foods: Occurrence and Legislation

by Abdellah Zinedine

Toxins 2010, 2(5), 1121-1133; https://doi.org/10.3390/toxins2051121 - 14 May 2010

Cited by 22 | Viewed by 10642

Abstract

Ochratoxin A (OTA) is secondary metabolite naturally produced in food and feed by toxigenic fungi, especially some Aspergillus species and Penicillium verucosum. OTA is one of the most studied mycotoxins and is of great interest due to its toxic effects on human [...] Read more.

Ochratoxin A (OTA) is secondary metabolite naturally produced in food and feed by toxigenic fungi, especially some Aspergillus species and Penicillium verucosum. OTA is one of the most studied mycotoxins and is of great interest due to its toxic effects on human and animals. OTA is produced in different food and feed matrices and contaminates a large range of base foods including cereals and derivatives, spices, dried fruits, wine and coffee, etc. Morocco, a North African country, has a climate characterized by high humidity and temperature, which probably favors the growth of molds. This contribution gives an overview of principal investigations about the presence of OTA in foods available in Morocco. Due to its toxicity, OTA presence is increasingly regulated worldwide, especially in countries of the European Union. However, up until now, no regulation limits were in force in Morocco, probably due to the ignorance of the health and economic problems resulting from OTA contamination. Finally, recommendations and future research directions are given required to assess the situation completely. Full article

(This article belongs to the Special Issue Ochratoxins)

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Open AccessReview

Ochratoxin A Producing Species in the Genus Penicillium

by Francisco Javier Cabañes, Maria Rosa Bragulat and Gemma Castellá

Toxins 2010, 2(5), 1111-1120; https://doi.org/10.3390/toxins2051111 - 14 May 2010

Cited by 92 | Viewed by 14573

Abstract

Ochratoxin A (OTA) producing fungi are members of the genera Aspergillus and Penicillium. Nowadays, there are about 20 species accepted as OTA producers, which are distributed in three phylogenetically related but distinct groups of aspergilli of the subgenus Circumdati and only in [...] Read more.

Ochratoxin A (OTA) producing fungi are members of the genera Aspergillus and Penicillium. Nowadays, there are about 20 species accepted as OTA producers, which are distributed in three phylogenetically related but distinct groups of aspergilli of the subgenus Circumdati and only in two species of the subgenus Penicillium. At the moment, P. verrucosum and P. nordicum are the only OTA producing species accepted in the genus Penicillium. However, during the last century, OTA producers in this genus were classified as P. viridicatum for many years. At present, only some OTA producing species are known to be a potential source of OTA contamination of cereals and certain common foods and beverages such as bread, beer, coffee, dried fruits, grape juice and wine among others. Penicillium verrucosum is the major producer of OTA in cereals such as wheat and barley in temperate and cold climates. Penicillium verrucosum and P. nordicum can be recovered from some dry-cured meat products and some cheeses. Full article

(This article belongs to the Special Issue Ochratoxins)

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Open AccessReview

Biodegradation of Ochratoxin A for Food and Feed Decontamination

by Luís Abrunhosa, Robert R.M. Paterson and Armando Venâncio

Toxins 2010, 2(5), 1078-1099; https://doi.org/10.3390/toxins2051078 - 13 May 2010

Cited by 184 | Viewed by 16742

Abstract

Ochratoxin A (OTA) is one of the most important mycotoxins that is found in food and feed products. It has proven toxic properties, being primarily known for its nephrotoxicity and carcinogenicity to certain animal species. OTA is produced by several species of Aspergillus [...] Read more.

Ochratoxin A (OTA) is one of the most important mycotoxins that is found in food and feed products. It has proven toxic properties, being primarily known for its nephrotoxicity and carcinogenicity to certain animal species. OTA is produced by several species of Aspergillus and Penicillium that can be found in a wide variety of agricultural products, which makes the presence of OTA in these products common. Many countries have statutory limits for OTA, and concentrations need to be reduced to as low as technologically possible in food and feed. The most important measures to be taken to control OTA are preventive in order to avoid fungal growth and OTA production. However, these measures are difficult to implement in all cases with the consequence of OTA remaining in agricultural commodities. Remediation processes are often used to eliminate, reduce or avoid the toxic effects of OTA. Biological methods have been considered increasingly as an alternative to physical and chemical treatments. However, examples of practical applications are infrequent. This review will focus on the (i) known microorganisms and enzymes that are able to biodegrade OTA; (ii) mode of action of biodegradation and (iii) current applications. A critical discussion about the technical applicability of these strategies is presented. Full article

(This article belongs to the Special Issue Ochratoxins)

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Ochratoxins in Feed, a Risk for Animal and Human Health: Control Strategies

by Muzaffer Denli and Jose F. Perez

Toxins 2010, 2(5), 1065-1077; https://doi.org/10.3390/toxins2051065 - 13 May 2010

Cited by 73 | Viewed by 11196

Abstract

Ochratoxin A (OTA) has been shown to be a potent nephrotoxic, hepatotoxic, and teratogenic compound. In farm animals, the intake of feed contaminated with OTA affects animal health and productivity, and may result in the presence of OTA in the animal products. Strategies [...] Read more.

Ochratoxin A (OTA) has been shown to be a potent nephrotoxic, hepatotoxic, and teratogenic compound. In farm animals, the intake of feed contaminated with OTA affects animal health and productivity, and may result in the presence of OTA in the animal products. Strategies for the control of OTA in food products require early identification and elimination of contaminated commodities from the food chain. However, current analytical protocols may fail to identify contaminated products, especially in animal feed. The present paper discusses the impact of OTA on human and animal health, with special emphasis on the potential risks of OTA residue in animal products, and control strategies applied in the feed industry. Full article

(This article belongs to the Special Issue Ochratoxins)

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Open AccessReview

Ochratoxin A in Ruminants–A Review on Its Degradation by Gut Microbes and Effects on Animals

by Muhammad Mobashar, Jürgen Hummel, Ralf Blank and Karl-Heinz Südekum

Toxins 2010, 2(4), 809-839; https://doi.org/10.3390/toxins204809 - 21 Apr 2010

Cited by 48 | Viewed by 12206

Abstract

Ruminants are much less sensitive to ochratoxin A (OTA) than non-ruminants. The ruminal microbes, with protozoa being a central group, degrade the mycotoxin extensively, with disappearance half lives of 0.6–3.8 h. However, in some studies OTA was detected systemically when using sensitive analytical [...] Read more.

Ruminants are much less sensitive to ochratoxin A (OTA) than non-ruminants. The ruminal microbes, with protozoa being a central group, degrade the mycotoxin extensively, with disappearance half lives of 0.6–3.8 h. However, in some studies OTA was detected systemically when using sensitive analytical methods, probably due to some rumen bypass at proportions of estimated 2–6.5% of dosage (maximum 10%). High concentrate proportions and high feeding levels are dietary factors promoting the likeliness of systemic occurrence due to factors like shifts in microbial population and higher contamination potential. Among risk scenarios for ruminants, chronic intoxication represents the most relevant. Full article

(This article belongs to the Special Issue Ochratoxins)

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Open AccessReview

Ochratoxins—Food Contaminants: Impact on Human Health

by Lalini Reddy and Kanti Bhoola

Toxins 2010, 2(4), 771-779; https://doi.org/10.3390/toxins2040771 - 20 Apr 2010

Cited by 120 | Viewed by 25314

Abstract

Ochratoxins are secondary metabolites of Aspergillus and Penicillium, that are hazardous to health through contamination of dietary foods. Ochratoxin A (OTA) remains the single most potent member of this group of mycotoxins. OTA has a long half-life in humans and is thus [...] Read more.

Ochratoxins are secondary metabolites of Aspergillus and Penicillium, that are hazardous to health through contamination of dietary foods. Ochratoxin A (OTA) remains the single most potent member of this group of mycotoxins. OTA has a long half-life in humans and is thus easily detected in serum. Dietary intake studies have confirmed link between endemic nephrotoxicity in humans to their daily household intake of OTA. OTA has been reported to contribute to endemic nephrotoxicity and carcinogenicity in humans and animals. OTA produces renal tumours, DNA adducts and chromosomal aberrations in kidneys. OTA may be embryotoxic, teratogenic, and immunotoxic only at doses higher than those causing nephrotoxicity. The incidence of endemic nephrotoxicity has been mostly reported in northeast Europe since the early fifties. Recent studies however have warned that OTA and other toxins, such as aristolochic acid, show very similar renal pathology. There is thus the need for thorough co-occurrence studies on toxin incidence. Full article

(This article belongs to the Special Issue Ochratoxins)

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Open AccessReview

Ochratoxin A: General Overview and Actual Molecular Status

by André El Khoury and Ali Atoui

Toxins 2010, 2(4), 461-493; https://doi.org/10.3390/toxins2040461 - 29 Mar 2010

Cited by 356 | Viewed by 26348

Abstract

Ochratoxin A (OTA) is a mycotoxin produced by several species of Aspergillus and Penicillium fungi that structurally consists of a para-chlorophenolic group containing a dihydroisocoumarin moiety that is amide-linked to L-phenylalanine. OTA is detected worldwide in various food and feed sources. Studies show [...] Read more.

Ochratoxin A (OTA) is a mycotoxin produced by several species of Aspergillus and Penicillium fungi that structurally consists of a para-chlorophenolic group containing a dihydroisocoumarin moiety that is amide-linked to L-phenylalanine. OTA is detected worldwide in various food and feed sources. Studies show that this molecule can have several toxicological effects such as nephrotoxic, hepatotoxic, neurotoxic, teratogenic and immunotoxic. A role in the etiology of Balkan endemic nephropathy and its association to urinary tract tumors has been also proved. In this review, we will explore the general aspect of OTA: physico-chemical properties, toxicological profile, OTA producing fungi, contaminated food, regulation, legislation and analytical methods. Due to lack of sufficient information related to the molecular background, this paper will discuss in detail the recent advances in molecular biology of OTA biosynthesis, based on information and on new data about identification and characterization of ochratoxin biosynthetic genes in both Penicillium and Aspergillus species. This review will also cover the development of the molecular methods for the detection and quantification of OTA producing fungi in various foodstuffs. Full article

(This article belongs to the Special Issue Ochratoxins)

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Response to Comments of Peter G. Mantle

by Gary G. Schwartz, Richard A. Manderville and Annie Pfohl-Leszkowicz

Toxins 2010, 2(10), 2337-2339; https://doi.org/10.3390/toxins2102337 - 29 Sep 2010

Cited by 10 | Viewed by 8150

Abstract

The apparently high yield of testis tumors (25%) in rats exposed long-term to Ochratoxin A (OTA) is uninterpretable without data on tumor yield in unexposed rats. Conversely, our demonstration that prenatal exposure to OTA induces DNA adducts in the testes of newborn mice [...] Read more.

The apparently high yield of testis tumors (25%) in rats exposed long-term to Ochratoxin A (OTA) is uninterpretable without data on tumor yield in unexposed rats. Conversely, our demonstration that prenatal exposure to OTA induces DNA adducts in the testes of newborn mice and the absence of these adducts in the testes of mice not exposed prenatally to OTA, is evidence for the presumptive carcinogenicity of OTA in the testis. Together with recent data showing that prenatal exposure to OTA depresses expression of DMRT1, a tumor suppressor gene in the testis, our findings suggest that OTA may be a cause of testicular cancer. Full article

(This article belongs to the Special Issue Ochratoxins)

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Open AccessCommentary

Comments on “Ochratoxin A: In utero Exposure in Mice Induces Adducts in Testicular DNA. Toxins 2010, 2, 1428–1444”—Mis-Citation of Rat Literature to Justify a Hypothetical Role for Ochratoxin A in Testicular Cancer

by Peter G. Mantle

Toxins 2010, 2(10), 2333-2336; https://doi.org/10.3390/toxins2102333 - 29 Sep 2010

Cited by 7 | Viewed by 8555

Abstract

A manuscript in the journal recently cited experimental rat data from two manuscripts to support plausibility of a thesis that ochratoxin A might be a cause of human testicular cancer. I believe that there is no experimental evidence that ochratoxin A produces testicular [...] Read more.

A manuscript in the journal recently cited experimental rat data from two manuscripts to support plausibility of a thesis that ochratoxin A might be a cause of human testicular cancer. I believe that there is no experimental evidence that ochratoxin A produces testicular cancer in rats or mice. Full article

(This article belongs to the Special Issue Ochratoxins)

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