Bioactivation in chemical teratogenesis.
Within the past decade, interest has increased markedly in the elucidation of mechanisms whereby drugs and other chemicals can alter the normal developmental pattern of the developing conceptus. This has, in large measure, been attributable to the recent availability of methods for the successful long-term culture of whole embryos as well as various embryonic tissues (e.g. limb buds). These preparations have enabled a more straightforward investigation of the direct effects of chemicals on the conceptus per se, without the complicating and frequently confounding participation of maternal factors. The demonstration that exogenous metabolic preparations could be incorporated into such culture systems has enabled investigators to pursue questions about the nature of proximate and ultimate chemical species responsible for producing abnormal morphogenesis. Demonstrations of the capacity of the early conceptus to effect profound dysmorphogenic bioactivation provide additional relevance to such questions. Elucidation of the identity of the chemical species represents a first and necessary step in unravelling the pathogenic mechanism. Control of their rates of generation and inactivation or elimination are probable major determinants of incidence/severity of chemically induced embryotoxicity. Future investigations of these phenomena promise to yield key contributions to the discovery of mechanisms in chemical teratogenesis.
Juchau
M R
MR
Department of Pharmacology, School of Medicine, University of Washington, Seattle 98195.
D000818:Animals; D001711:Biotransformation; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D006801:Humans; D011247:Pregnancy; D013723:Teratogens / Q000378:metabolism*
D013723:Teratogens