Temporal patterns of DNA adduct formation and glutathione S-transferase activity in the testes of rats fed aflatoxin B-1: A comparison with patterns in the liver

Fisher-344 male rats were fed 1.6 ppm of aflatoxin B-1 (AFB(1)) continuousl y and intermittently For several weeks. At various time periods, DNA was is olated from the testes and livers and analyzed for AFB(1)-DNA adducts. The ability of the testis to detoxify AFB(1) was also investigated by the gluat hione S-transferase (GST) activity assay and compared with that of the live r. The levels of testicular AFB(1)-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 tes ticular DNA adducts markedly decreased over time. By 16 weeks of continuous and 20 weeks of intermittent exposure, they had decreased 37 and 91%, resp ectively. In contrast, hepatic AFB(1)-DNA adducts increased four-fold from 4 to 16 weeks of continuous treatment but increased at a much slower rate a fter intermittent exposure. In both the liver and testis, significant level s of AFB(1)-DNA adducts persisted for at least 1 month after ending the tre atment, suggesting that this type of lesion was poorly repaired. In control rots, the testis showed significantly higher GST activity than the liver. In treated rots, these differences were significant during the first 12 wee ks of continuous treatment but not at later times. Tissue-specific differen ces 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. Environ. Mel. Mutagen. 33. 293-302, 1999 (C) 1999 Wiley-Liss, Inc.