Carbon monoxide inhibits monooxygenation by the conceptus and embryotoxic effects of proteratogens in vitro.
Evidence that Day 10 to 11 rat conceptuses can contain sufficient quantities of xenobiotic-oxidizing P-450(s) to catalyze the conversion of proteratogens to reactive teratogenic intermediates is presented. Quantities of reactive intermediates generated by conceptuses from 2-acetylaminofluorene (AAF) were sufficient to result in the appearance of gross morphologic abnormalities with a high incidence of neural tube anomalies. Carbon monoxide effectively inhibited the conversion of AAF to hydroxylated metabolites by rat conceptuses, and also inhibited the capacity of AAF to elicit neural tube anomalies in cultured embryos. Inhibition by CO of either parameter was observed only with conceptuses exposed in utero to the potent P-450 inducer, 3-methylcholanthrene.
Faustman-Watts
E M
EM
Giachelli
C M
CM
Juchau
M R
MR
D015073:2-Acetylaminofluorene / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D002248:Carbon Monoxide / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D008748:Methylcholanthrene / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D010105:Oxygenases / Q000037:antagonists & inhibitors*; D011247:Pregnancy; D051381:Rats; D013723:Teratogens / Q000037:antagonists & inhibitors* / Q000378:metabolism
D013723:Teratogens; D008748:Methylcholanthrene; D002248:Carbon Monoxide; D003577:Cytochrome P-450 Enzyme System; D015073:2-Acetylaminofluorene; D010105:Oxygenases