Temporal patterns of DNA adduct formation and glutathione S-transferase activity in the testes of rats fed aflatoxin B1: a comparison with patterns in the liver.
Fisher-344 male rats were fed 1.6 ppm of aflatoxin B1 (AFB1) continuously and intermittently for several weeks. At various time periods, DNA was isolated from the testes and livers and analyzed for AFB1-DNA adducts. The ability of the testis to detoxify AFB1 was also investigated by the glutathione S-transferase (GST) activity assay and compared with that of the liver. The levels of testicular AFB1-DNA adducts were 2.4 to 8.1 times lower than those of the liver after 4 to 16 weeks of continuous treatment and 2.2 to 46.2 times lower after 8 to 20 weeks of intermittent treatment. The testicular DNA adducts markedly decreased over time. By 16 weeks of continuous and 20 weeks of intermittent exposure, they had decreased 37 and 91%, respectively. In contrast, hepatic AFB1-DNA adducts increased four-fold from 4 to 16 weeks of continuous treatment but increased at a much slower rate after intermittent exposure. In both the liver and testis, significant levels of AFB1-DNA adducts persisted for at least 1 month after ending the treatment, suggesting that this type of lesion was poorly repaired. In control rats, the testis showed significantly higher GST activity than the liver. In treated rats, these differences were significant during the first 12 weeks of continuous treatment but not at later times. Tissue-specific differences such as germ-cell depletion and increased testicular detoxification may play an important role in the observed differential pattern of DNA adduct formation between the testis and liver.
Center for Food Safety and Applied Nutrition, Food and Drug Administration, Laurel, Maryland, USA. res@cfsan.fda.gov
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Sotomayor
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Sahu
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Washington
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Hinton
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Chou
D016604:Aflatoxin B1 / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts / Q000378:metabolism; D004032:Diet; D005982:Glutathione Transferase / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D008297:Male; D009153:Mutagens / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D013737:Testis / Q000187:drug effects* / Q000201:enzymology
D018736:DNA Adducts; D009153:Mutagens; C072611:aflatoxin B1-DNA adduct; D016604:Aflatoxin B1; D005982:Glutathione Transferase