Benzo[e]pyrene pretreatment of immature, female C57BL/6J mice results in increased bioactivation of aflatoxin B1 in vitro.
Hepatic microsomes were prepared from immature C57BL/6J mice 24 h after receiving intraperitoneal injections of either corn oil, benzo[e]pyrene (BeP, 50 mg/kg) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 4 x 10(-3) mg/kg). The capacity of these hepatic microsomes to bioactivate aflatoxin B1 (AFB1), 2-aminoanthracene (AA), benzo[a]pyrene (BaP), 3-methylcholanthrene (MC), 7,12-dimethylbenzanthracene (DMBA), BeP and pyrene (PY) was measured using strain TA100 in the Salmonella typhimurium/microsome reversion assay. BeP pretreatment of mice resulted in a 33% increase in mutagenic potency (MP) of AFB1 over the corn oil controls and a 70% increase in MP relative to TCDD-pretreated microsomes. With AA, BaP and DMBA as promutagens, BeP pretreatment reduced MP an average of 24%, while TCDD pretreatment increased MP of these 3 promutagens 263% compared to controls. Since the general effects of BeP and TCDD on murine hepatic cytochrome P-450 (P450)-mediated activities in this study were discordant, it appears that changes in P450 activity by BeP pretreatment are not mediated through the Ah receptor.
Ma
X F
XF
Department of Pharmacology, New York State College of Veterinary Medicine, Cornell University, Ithaca 14853.
Gibbons
J A
JA
Babish
J G
JG
D016604:Aflatoxin B1 / Q000493:pharmacokinetics* / Q000633:toxicity; D000818:Animals; D001580:Benzopyrenes / Q000633:toxicity*; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009152:Mutagenicity Tests; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity; D012486:Salmonella typhimurium / Q000187:drug effects
D001580:Benzopyrenes; D000072317:Polychlorinated Dibenzodioxins; C026487:benzo(e)pyrene; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1