期刊
ARHIV ZA HIGIJENU RADA I TOKSIKOLOGIJU-ARCHIVES OF INDUSTRIAL HYGIENE AND TOXICOLOGY
卷 63, 期 4, 页码 417-427出版社
INST MEDICAL RESEARCH & OCCUPATIONAL HEALTH
DOI: 10.2478/10004-1254-63-2012-2202
关键词
bioactivation; carcinogenicity; DNA adduction; glutathione; metabolism; mutagenicity; N-acetylcysteine
资金
- European Union [QLK1-2001-01614]
- Region Midi-Pyrenees
- French Ministry of Research
- Association recherche centre cancer (ARC)
- Natural Sciences and Engineering Research Council of Canada (NSERC)
- Canadian Foundation for Innovation (CFI)
- Ontario Innovation Trust Fund (OIT)
- Delphine Canadas
In the present study the photoreactivity of the fungal carcinogen ochratoxin A (OTA) has been utilised to generate authentic samples of reduced glutathione (GSH) and N-acetylcysteine (NAC) conjugates of the parent toxin. These conjugates, along with the nontoxic OT alpha, which is generated through hydrolysis of the amide bond of OTA by carboxypeptidase A, were utilised as biomarkers to study the metabolism of OTA in the liver and kidney of male and female Dark Agouti rats. Male rats are more susceptible than female rats to OTA carcinogenesis with the kidney being the target organ. Our studies show that the distribution of OTA in male and female rat kidney is not significantly different. However, the extent of OTA metabolism was greater in male than female rats. Much higher levels of OT alpha were detected in the liver compared to the kidney, and formation of OT alpha is a detoxification pathway for OTA. These findings suggest that differences in metabolism between male and female rats could provide an explanation for the higher sensitivity of male rats to OTA toxicity.
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