Drug metabolizing enzymes in Drosophila melanogaster: teratogenicity of cyclophosphamide in vitro.
This report concerns the attempt to demonstrate the practicability of using microsomal fractions (rat or Drosophila) for activating proteratogens in a Drosophila in vitro teratogen screening assay. Accordingly, a typical proteratogen (cyclophosphamide) was tested before and after microsomal activation and results compared with the drug directly on the in vitro assay. The effects of microsomal activation on known teratogens (thalidomide) and nonteratogens (acetaminophen) were also assayed in order to determine the specificity of the activation process. The results showed activation of the proteratogen into a teratogen occurred as in comparable systems. Activation was specific as teratogens and nonteratogens were not altered in the assay. These preliminary results represent the first direct demonstration that the Drosophila microsomal fraction is capable of bioactivating a proteratogen. This capability further extends the usefulness of the Drosophila embryonic culture assay as an in vitro screen for potential teratogens.
D000082:Acetaminophen / Q000633:toxicity; D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000378:metabolism / Q000633:toxicity*; D004331:Drosophila melanogaster / Q000201:enzymology*; D008861:Microsomes / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism; D013723:Teratogens / Q000378:metabolism*; D013792:Thalidomide / Q000633:toxicity
D013723:Teratogens; D000082:Acetaminophen; D013792:Thalidomide; D003520:Cyclophosphamide; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases