Effects of amitraz on cytochrome P450-dependent monooxygenases and estrogenic activity in MCF-7 human breast cancer cells and immature female rats.
This study investigated the ability of amitraz, a formamidine insecticide, to induce cytochrome P450-dependent monooxygenases and to disrupt estrogenic activity in human breast cancer MCF-7 cells and immature female rats. In MCF-7 cells, treatment with 10 microM amitraz for 24 h increased 7-ethoxyresorufin O-deethylase activity in cell homogenate. Treatment of MCF-7 cells with 1 and 10 microM amitraz for 3 h replaced previously bound [(3)H]17beta-estradiol (E(2)) from estrogen receptors. Treatment with 0.1 and 1 microM amitraz for 2 days inhibited [(3)H]thymidine incorporation into the DNA of MCF-7 cells while the inhibition was blocked in cells co-treated with 1 nM E(2) and amitraz. In immature female rats, treatment with 50 mg/kg amitraz intraperitoneally for 3 days increased cytochrome P450 content, 7-ethoxyresorufin, methoxyresorufin and pentoxyresorufin O-dealkylases, and benzo[a]pyrene hydroxylase activities in liver microsomes. The results of immunoblot analysis revealed that amitraz induced liver microsomal CYP1A1/2, 2B1/2B2, and 3A proteins. Treatment with 10 and 25 mg/kg amitraz for 3 days dose-dependently decreased uterine weight and peroxidase activity in immature female rats while the decreases were blocked in rats co-treated with 10 microg/kg E(2) and 10 or 25 mg/kg amitraz. These in vitro and in vivo findings suggest that amitraz induces multiple forms of P450 and exerts weak antiestrogenic activity.
Ueng
Tzuu-Huei
TH
Institute of Toxicology, College of Medicine, National Taiwan University, 1 Jen Ai Road, Section 1, Taipei, Taiwan, ROC. thueng@ha.mc.ntu.edu.tw
Hung
Chia-Chi
CC
Wang
Hui-Wu
HW
Chan
Ping-Kun
PK
D000818:Animals; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D004958:Estradiol / Q000378:metabolism; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D007306:Insecticides / Q000494:pharmacology; D008099:Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000187:drug effects* / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism*; D014052:Toluidines / Q000494:pharmacology*; D014599:Uterus / Q000187:drug effects* / Q000201:enzymology
D020847:Estrogen Receptor Modulators; D007306:Insecticides; D011960:Receptors, Estrogen; D014052:Toluidines; C014983:amitraz; D004958:Estradiol; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D009195:Peroxidase; D019363:Cytochrome P-450 CYP1A1