Effect of frying-meat emission particulate on 17beta-estradiol 2- and 4-hydroxylation in human lung adenocarcinoma CL5 cells.

The effect of airborne frying-meat emission particulate (FMEP) on metabolism of 17beta-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 CLS cells or cells treated with 200 mug/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 muM dibenz[a,h]anthracene. Cotreatment of CL5 cells with FMEP extract and 2 muM alpha-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 muM alpha-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 by human lung 2 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.