Role of cytochrome P450 1A1 and 1B1 in metabolic activation of dibenzo[a,l]pyrene by microsomes from the human mammary carcinoma cell line MCF-7

Incubation of DB[a,l]P with microsomes from TCDD-treated MCF-7 cells produc ed mainly (-) anti DB[a,l]P-11,12-diol 13,14-epoxide-dAdo adducts. Addition of antibodies against CYP1A1 and CYP1B1 inhibited the formation of DNA add ucts up to 88% and 51%, respectively. The level of P450 1B1 protein was dra matically elevated, but P450 1A1 protein is not detectable by blottings in MCF-7 cells treated with 5 mu M or 8 mu M DB[a,l]. MCF-7 cells treated with TCDD or B[a]P contained elevated P450 1A1 and P450 1B1. The current result s demonstrate that both P450 1A1 and P450 1B1 are involved in metabolic act ivation of DB [a,l]P in MCF-7 cells treated with TCDD and suggest that P450 1B1 may be the major DB [a,l]P activating enzyme in MCF-7 cells treated wi th DB[a,l]P.