In vitro metabolism of diethylstilbestrol by hepatic, renal and uterine microsomes of rats and hamsters. Effects of different inducers.
In order to elucidate possible differences in the metabolism of the synthetic estrogen diethylstilbestrol (DES) by target and non-target tissues for DES carcinogenicity, the biotransformation of [14C]DES has been studied in vitro with hepatic and renal microsomes of male and female hamsters and rats, and from hamster and rat uterus. Of these tissues, only the male hamster kidney is susceptible to the carcinogenic effect of DES. Moreover, the effect of various inducers on the in vitro metabolism of DES has been investigated. It was found that male hamster kidney microsomes produced a markedly different pattern of DES metabolites as compared to renal microsomes from female hamster or male and female rats. Pretreatment with phenobarbital markedly increased oxidative DES metabolism by renal microsomes from female rat but not from male rat. Diethylstilbestrol metabolism by hepatic microsomes was different between hamster and rat, but was not sex-dependent and could not be significantly affected by pretreatment with phenobarbital, DES, 3-methylcholanthrene and 7:8-benzoflavone. The differences in DES metabolism between target and non-target organs and its modulation by inducers may help to gain further insight into the mechanism of DES tumorigenesis.
D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D004054:Diethylstilbestrol / Q000378:metabolism* / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D008647:Mesocricetus; D008748:Methylcholanthrene / Q000494:pharmacology; D008861:Microsomes / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014599:Uterus / Q000378:metabolism*
D001571:Benzoflavones; D008748:Methylcholanthrene; C011512:alpha-naphthoflavone; D004054:Diethylstilbestrol; D010634:Phenobarbital