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

• Published in: Polycyclic aromatic compounds Vol. 16; no. 1-4; pp. 109 - 118
• Main Authors: Cai, Yingna, Marcus, Craig, Guengerich, F. Peter, Gelboin, Harry V., Baird, William M.
• Format: Journal Article
• Language: English
• Published: Taylor & Francis Group 01.06.2000
• Subjects: Cytochrome P450; dibenzo[a,l]pyrene; DNA adducts; human mammary carcinoma cell line
• ISSN: 1040-6638; 1563-5333
• DOI: 10.1080/10406639908020578

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.