Differential effects of butylated hydroxyanisole on metabolism of aflatoxin B1 in vitro by liver and lung microsomes.
Growing epidemiological evidence points out the carcinogenic hazard of inhaled aflatoxin B1 (AFB1) to the pulmonary system. Metabolism of AFB1 by lung microsomes and its binding to calf thymus DNA are reported for the first time in this paper. In addition, the ability of dietary butylated hydroxyanisole (BHA) to modulate AFB1 adduct formation with DNA was examined. Lung microsomes from BHA-treated rats unlike those from liver caused a 50% inhibition of AFB1-DNA binding. However, pulmonary cytosolic glutathione (GSH) S-transferase activity remained unaltered. The addition of BHA-treated lung cytosol failed to produce a greater inhibition of AFB1-DNA binding than control cytosol. Microsome mediated AFB1-DNA binding was markedly inhibited (30%) by the addition of GSH alone to the incubation system. Further addition of cytosol contributed much less (10%) to the inhibition of AFB1-DNA binding. These observations together with the induction of microsomal GSH S-transferase strongly implicate the role of microsomal GSH S-transferase in the modulation of AFB1-DNA binding.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002083:Butylated Hydroxyanisole / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D005982:Glutathione Transferase / Q000378:metabolism; D008658:Inactivation, Metabolic / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000348:Aflatoxins; D002083:Butylated Hydroxyanisole; D004247:DNA; D016604:Aflatoxin B1; D005982:Glutathione Transferase