Effect of Frying-Meat Emission Particulate On 17β-Estradiol 2- and 4-Hydroxylation in Human Lung Adenocarcinoma Cl5 Cells

Abstract

The effect of airborne frying-meat emission particulate (FMEP) on metabolism of 17 g -estradiol (E 2 ) to potentially toxic catechol estrogens 2- and 4-hydroxyestradiol (2- and 4-OH-E 2 ) was determined using human lung adenocarcinoma CL5 cells treated with organic extracts of beef FMEP. E 2 was incubated with microsomes prepared from untreated CL5 cells or cells treated with 200 w g/ml FMEP extract for 6 h. E 2 metabolites formed were analyzed by high-performance liquid chromatography (HPLC). The results revealed that treatment with FMEP produced three-and twofold increases of 2- and 4-hydroxylation of E 2 , respectively. Monooxygenase activity and immunoblot analyses showed that FMEP markedly induced microsomal 7-ethoxyresorufin O-deethylase (EROD) activity and cytochrome P-450 (CYP) IAI and CYPIBI protein levels. Similar increases in E 2 hydroxylation, EROD activity, and CYP protein levels were observed with HepG2 human hepatoma and MCF-7 human breast cancer cells treated with FMEP or 1 w M dibenz[a,h]anthracene. Cotreatment of CL5 cells with FMEP extract and 2 w M f -naphthoflavone, an arylhydrocarbon receptor antagonist, blocked the inductive effects of FMEP on E 2 hydroxylation and EROD activity. Additions of 0.01, 0.1, or 1 w M f -naphthoflavone, a CYP inhibitor, to microsomes produced concentration-dependent decreases in E 2 2-hydroxylation and EROD activity of CL5 cells induced by dibenz[a,h]anthracene. The present finding demonstrates that FMEP can increase formation of 2-OH-E 2 and 4-OH-E 2 by human lung cells, and induction of CYP1A1 and CYP1B1 is a potential mechanism underlying increased E 2 metabolism. The toxicological significance of FMEP and estrogen interaction warrants further investigation.