Antiestrogenic effects of motorcycle exhaust particulate in MCF-7 human breast cancer cells and immature female rats.
The emissions from 2- and 4-stroke motorcycles pollute the air of urban areas where motorcycle is a popular means of transportation. This study aimed to determine the endocrine-disrupting activity of motorcycle exhaust particulate (MEP) using MCF-7 human breast cancer cells and immature female Wistar rats treated with organic extracts of MEP. Treatments with 1, 10, and 50 microg/ml MEP extract for 2 and 4 days produced dose-dependent inhibition of thymidine incorporation and cell growth, respectively, in untreated and 1 nM 17beta-estradiol (E2)-treated cells. Treatments of MCF-7 cells with MEP extract replaced [3H]E2 from the estrogen receptor in a time- and concentration-dependent manner. These antiestrogenic and receptor binding properties of MEP extract were blocked by cotreatment of the cells with 2 microM alpha-naphthoflavone, a cytochrome P450 inhibitor and aryl hydrocarbon receptor antagonist. E2 metabolism and HPLC analysis showed that treatment of MCF-7 cells with 50 microg/ml MEP extract for 24 h increased E2 2- and 4-hydroxylation in microsomes. The MEP-mediated increase in E2 2-hydroxylation was inhibited by the addition of 1 microM alpha-naphthoflavone to MCF-7 microsomes. Cotreatment of immature female rats with 10 microg/kg E2 and 10 mg/kg MEP extract intraperitoneally for 3 days decreased the E2-induced uterine weights. MEP extract alone showed no effect on rat uterine weight. The endocrine-disrupting activity of MEP extract was further confirmed in parallel experiments using MCF-7 cells and immature female rats treated with benzo(a)pyrene, an MEP constituent compound. The present findings demonstrate that MEP extract is antiestrogenic in vitro and in vivo and cytochrome P450 induction is an underlying mechanism.
Ueng
Tzuu-Huei
TH
Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, ROC. thueng@ha.mc.ntu.edu.tw
Wang
Hui-Wu
HW
Huang
Yu-Ping
YP
Hung
Chia-Chi
CC
D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity; D001571:Benzoflavones / Q000633:toxicity; D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D004958:Estradiol / Q000633:toxicity; D020847:Estrogen Receptor Modulators / Q000633:toxicity*; D047628:Estrogen Receptor alpha; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D009049:Motorcycles; D009929:Organ Size / Q000187:drug effects; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000378:metabolism*; D014599:Uterus / Q000187:drug effects*; D001335:Vehicle Emissions / Q000633:toxicity*
D000393:Air Pollutants; D001571:Benzoflavones; D065607:Cytochrome P-450 Enzyme Inhibitors; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen; D001335:Vehicle Emissions; D001564:Benzo(a)pyrene; D004958:Estradiol; C011512:alpha-naphthoflavone; D003577:Cytochrome P-450 Enzyme System