Role of estrogen receptor in regulation of polycyclic aromatic hydrocarbon metabolic activation in lung

Epidemiological and biochemical studies have indicated that females may be at greater risk of smoking associated lung cancer compared with mates. Among lung cancer patients, female smokers have been found to have higher levels of PAH-related DNA adducts and CYP1A1 gene expression in their normal lung tissue compared to mate smokers. A possible rote of steroid hormones in these sex differences via interactions between aryl. hydrocarbon receptor and estrogen receptor mediated cellular effects has been suggested. In the present study the impact of the estrogen receptor (ERalpha) on CYP1A1 and CYP1B1 gene expression was studied in vitro in human bronchial epithelial. cells. Transient transfection of the BEP2D cell tine with ERalpha influenced neither constitutive expression of CYP1A1 or CYP1B1 nor induction of these genes by TCDD as measured by real-time RT-PCR. ERalpha had no effect on the constitutive or TCDD-induced enzymatic activity of CYP1A1 (EROD). We also studied the effect of steroid hormones on lung PAH metabolic activation in A/J mice. Intact and ovariectomized female mice were orally exposed to a single dose of benzo[alpha]pyrene. Ovariectomy did not influence the levels of either benzo[alpha]pyrene-derived protein or DNA adducts in the lung tissue measured by HPLC and P-32-postlabeling, respectively. In conclusion, the present data do not support the hypothesis of a role of estrogen or the ERalpha in regulating the metabolic activation of polycyclic aromatic hydrocarbons in lung. (C) 2004 Elsevier Ireland Ltd. All rights reserved.