Metabolism of phenytoin in teratogenesis-susceptible and -resistant strains of mice.
Phenytoin (PHT) is teratogenic in A/J but not in C57BL/6J mice. Teratogenesis in F1 hybrid offspring of these two strains is dependent on the susceptibility of the maternal parent. Hepatic microsomes from untreated pregnant A/J females produced more of both the phenolic and diol metabolites than did microsomes from pregnant C57BL/6J females. This difference disappeared when the animals were pretreated with phenobarbital or phenytoin. It seems unlikely that the genetic difference in susceptibility to PHT-induced teratogenesis can be explained on the basis of maternal metabolism of the drug.
D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004351:Drug Resistance; D005260:Female; D008297:Male; D008431:Maternal-Fetal Exchange; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D010672:Phenytoin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D011247:Pregnancy; D012737:Sex Factors; D013045:Species Specificity; D013723:Teratogens / Q000378:metabolism*; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D013723:Teratogens; C001419:hydroxyphenytoin; C027363:5-(3,4-dihydroxy-1,5-cyclohexadien-1-yl)-5-phenylhydantoin; D019324:beta-Naphthoflavone; D010672:Phenytoin; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital