Ma X F, Gibbons J A, Babish J G
Department of Pharmacology, New York State College of Veterinary Medicine, Cornell University, Ithaca 14853.
Toxicol Lett. 1991 Dec;59(1-3):51-8. doi: 10.1016/0378-4274(91)90054-a.
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.
在给未成熟的C57BL/6J小鼠腹腔注射玉米油、苯并[e]芘(BeP,50毫克/千克)或2,3,7,8-四氯二苯并对二恶英(TCDD,4×10⁻³毫克/千克)24小时后,制备肝微粒体。使用鼠伤寒沙门氏菌/微粒体回复突变试验中的TA100菌株,测定这些肝微粒体对黄曲霉毒素B1(AFB1)、2-氨基蒽(AA)、苯并[a]芘(BaP)、3-甲基胆蒽(MC)、7,12-二甲基苯并蒽(DMBA)、BeP和芘(PY)的生物活化能力。用BeP预处理小鼠后,与玉米油对照组相比,AFB1的诱变效力(MP)增加了33%,相对于用TCDD预处理的微粒体,MP增加了70%。以AA、BaP和DMBA作为前诱变剂时,BeP预处理使MP平均降低了24%,而TCDD预处理使这3种前诱变剂的MP相对于对照组增加了263%。由于在本研究中BeP和TCDD对小鼠肝细胞色素P-450(P450)介导的活性的总体影响不一致,因此看来BeP预处理引起的P450活性变化不是通过芳烃受体介导的。