Role of CYP1B1 in PAH-DNA Adduct Formation and Breast Cancer Risk

The cytochrome P450 enzyme CYP1B1 is a major enzyme involved in metabolizing polycyclic aromatic hydrocarbons (PAHs) to reactive intermediates. Given that exposure to carcinogenic PAHs may be a breast cancer risk factor, we have set out to investigate molecular mechanisms of the relationship between...

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Bibliographic Details
Main Author: Goth-Goldstein, Regine
Format: Report
Language:English
Subjects:
Anatomy and Physiology
AROMATIC HYDROCARBONS
BREAST CANCER
COSTS
CYP1B1
DEOXYRIBONUCLEIC ACIDS
DNA ADDUCTS
ENZYMES
GENE EXPRESSION
Genetic Engineering and Molecular Biology
GENETIC POLYMORPHISM
MAMMARY GLANDS
METABOLISM
MOLECULAR PROPERTIES
PAH(POLYCYCLIC AROMATIC HYDROCARBONS)
POLYCYCLIC COMPOUNDS
RISK
SURGERY
TISSUES(BIOLOGY)
XENOBIOTIC METABOLISM
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Summary:The cytochrome P450 enzyme CYP1B1 is a major enzyme involved in metabolizing polycyclic aromatic hydrocarbons (PAHs) to reactive intermediates. Given that exposure to carcinogenic PAHs may be a breast cancer risk factor, we have set out to investigate molecular mechanisms of the relationship between PAH exposure, CYP1B1 expression and breast cancer risk in a clinic-based case-control study. We have collected nontumor breast tissue from 43 women (32 cases and 11 controls) undergoing surgery and analyzed these specimens for CYP1B1 gene expression, CYP1B1 genotype and PAH-DNA adducts. CYP1B1 transcript levels determined by quantitative RT-PCR, varied more than 1000-fold between individuals. DNA adduct levels varied 10-fold between individuals. Because of the delayed start of the project, we have applied for and obtained a no cost extension until 10/27/07.