Teratology testing: I. Development and status of short-term prescreens. II. Biotransformation of teratogens as studied in whole embryo culture.
The development and role of short-term prescreening tests have been described and discussed in the first section. In the second section we have summarized the results of studies of the biotransformation and bioactivation of teratogens in a whole embryo culture system. The effect of adding a hepatic monooxygenase with or without cofactors or inhibitors gives information on the phase I bioactivation of teratogens. The growth retardation and defect rate can be correlated with the concentration of teratogen added. Four teratogens (cyclophosphamide, chlorambucil, rifampicin, and 2-acetylaminofluorene) were bioactivated in vitro by a liver monooxygenase system; one (cytochalasin D) was inactivated and seven others were active without bioactivation. Those that were active without bioactivation were sodium salicylate, niridazole, phosphoramide mustard, acrolein, 4-hydroperoxycyclophosphamide, 4-ketocyclophosphamide, ethanol, and acetaldehyde. These results establish that biotransformational variables must be considered if mass-screening programs are to have any validity.
D000818:Animals; D001711:Biotransformation; D004622:Embryo, Mammalian / Q000378:metabolism*; D004625:Embryo, Nonmammalian; D005260:Female; D008099:Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009924:Organ Culture Techniques; D011247:Pregnancy; D013723:Teratogens / Q000378:metabolism / Q000633:toxicity*; D014116:Toxicology / Q000379:methods
D013723:Teratogens; D006899:Mixed Function Oxygenases