Cytochrome P4501B1 Expression in Normal Breast Tissue

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are metabolically activated to ultimate carcinogens by the cytochrome P-450 isozymes CYP1A1 and CYP1B1. High levels of these enzymes may result in increased DNA adduct formation and cancer initiation. We investigated whether expression of CYP1B1 in breast tissue varies to a similar extent as has been shown for CYP1A1 and whether increased CYP1B1 expression could constitute a risk factor for breast cancer. Expression of CYP1B1 and CYP1A1 was measured in a collection of 75 nontumor epithelial breast tissue specimens from breast cancer patients ( n = 36) and from cancer-free individuals ( n = 39). Using a semiquantitative reverse transcription (RT)-polymerase chain reaction (PCR) assay, CYP1B1 and CYP1A1 expression levels relative to the constantly expressed g - actin gene were determined. In this study, we found 300-fold and 1,000-fold interindividual variation in expression for CYP1B1 and CYP1A1 , respectively. The mean CYP1B1 transcript level in normal breast tissue was 70% higher in mastectomy patients compared with cancer-free individuals ( p = .0473). These data suggest that CYP1B1 may play a role in breast cancer etiology, particularly in women exposed to high levels of CYP1B1 substrates such as PAHs.