Effects of four organohalogen environmental contaminants on cytochrome P450 forms that catalyze 4- and 2-hydroxylation of estradiol in the rat liver.
The four environmental pollutants studied (3,3',4,4',5-pentachlorobiphenyl, 2,2',4,4'-tetrabromodiphenyl ether, Tris-(p-chlorophenyl)methanol, and 3,4,5-trichloroguaiacol) were all found to induce a significant increase in 4-hydroxylation of estradiol activity in male rat liver microsomes. However, only 3,3',4,4',5-pentachlorobiphenyl was found to significantly increase 4- and 2-hydroxylation of estradiol in female rat liver microsomes. 4-Hydroxylation has been suggested to be responsible for the development of estrogen-dependent tumors and, therefore, it cannot be excluded that these pollutants can be a risk for the development of estrogen-dependent tumors in humans and wildlife.
Segura-Aguilar
J
J
Department of Pharmaceutical Bioscience, Uppsala University, Sweden.
Castro
V
V
Bergman
A
A
D000818:Animals; D001943:Breast Neoplasms / Q000209:etiology; D002274:Carcinogens, Environmental / Q000633:toxicity; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004785:Environmental Pollutants / Q000633:toxicity*; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D006139:Guaiacol / Q000031:analogs & derivatives / Q000633:toxicity; D055768:Halogenated Diphenyl Ethers; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000633:toxicity; D006846:Hydrocarbons, Halogenated / Q000633:toxicity*; D006900:Hydroxylation; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism*; D009376:Neoplasms, Hormone-Dependent / Q000209:etiology; D010647:Phenyl Ethers / Q000633:toxicity; D011075:Polybrominated Biphenyls; D011078:Polychlorinated Biphenyls / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D014320:Triphenylmethyl Compounds / Q000633:toxicity
D002274:Carcinogens, Environmental; D004785:Environmental Pollutants; D055768:Halogenated Diphenyl Ethers; D006842:Hydrocarbons, Brominated; D006846:Hydrocarbons, Halogenated; D010647:Phenyl Ethers; D011075:Polybrominated Biphenyls; D014320:Triphenylmethyl Compounds; C511295:2,2',4,4'-tetrabromodiphenyl ether; C104274:tris(4-chlorophenyl)methanol; D004958:Estradiol; C068682:3,4,5-trichloroguaiacol; D006139:Guaiacol; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; C023035:3,4,5,3',4'-pentachlorobiphenyl