Roles 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

Abstract

Incubation of DB[a, l]P with microsomes from TCDD-treated MCF-7 cells produced 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 adducts up to 88% and 51%, respectively. The level of P450 1B1 protein was dramatically elevated, but P450 1A1 protein is not detectable by blottings in MCF-7 cells treated with 5 μM or 8 μM DB[a, l]P. MCF-7 cells treated with TCDD or B[a]P contained elevated P450 1A1 and P450 1B1. The current results demonstrate that both P450 1A1 and P450 1B1 are involved in metabolic activation 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 with DB[a, l]P.