Effect of frying-meat emission particulate on 17β-estradiol 2- and 4-hydroxylation in human lung adenocarcinoma CL5 cells
Journal
Journal of Toxicology and Environmental Health - Part A
Journal Volume
66
Journal Issue
12
Pages
1175-1188
Date Issued
2003
Author(s)
Abstract
The effect of airborne frying-meat emission particulate (FMEP) on metabolism of 17β-estradiol (E2) to potentially toxic catechol estrogens 2- and 4-hydroxyestradiol (2- and 4-OH-E2) was determined using human lung adenocarcinoma CL5 cells treated with organic extracts of beef FMEP. E2 was incubated with microsomes prepared from untreated CL5 cells or cells treated with 200 μg/ml FMEP extract for 6 h. E2 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 E2, 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 E2 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 μM dibenz[a,h]anthracene. Cotreatment of CL5 cells with FMEP extract and 2 μM α-naphthoflavone, an arylhydrocarbon receptor antagonist, blocked the inductive effects of FMEP on E2 hydroxylation and EROD activity. Additions of 0.01, 0.1, or 1 μM α-naphthoflavone, a CYP inhibitor, to microsomes produced concentration-dependent decreases in E2 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-E2 and 4-OH-E2 by human lung cells, and induction of CYP1A1 and CYP1B1 is a potential mechanism underlying increased E2 metabolism. The toxicological significance of FMEP and estrogen interaction warrants further investigation.
SDGs
Other Subjects
alpha naphthoflavone; cytochrome P450 1A1; cytochrome P450 1B1; dibenz[a,h]anthracene; estradiol; ethoxyresorufin deethylase; polycyclic aromatic hydrocarbon; toxic substance; airborne particle; article; carcinoma cell; concentration response; frying; high performance liquid chromatography; human; human cell; hydroxylation; lung adenocarcinoma; meat; mutagenicity; oxidative stress; particulate matter; priority journal; tumor growth; Adenocarcinoma; Adult; Aryl Hydrocarbon Hydroxylases; Cookery; Cytochrome P-450 CYP1A1; Cytochrome P-450 Enzyme System; Estradiol; Female; Humans; Hydroxylation; Lung Neoplasms; Tumor Cells, Cultured; Mink cell focus-forming virus
Type
journal article