Development of an in vitro system detecting pro-embryotoxin.
An in vitro system for detection of embryotoxins has been developed by using primary cultures of embryo fibroblasts. Various embryotoxins, including benzo[a]pyrene and thalidomide, have trivial cytotoxicity in embryo fibroblast systems, which is at least in part due to a lack of capacity for metabolic activation. Introduction of steps for microsomal pre-incubation and calcium-precipitation prior to chemical contact resulted in the clear appearance of embryotoxicity toward thalidomide and benzo[a]pyrene. This pre-incubation method will offer advantages for the detection of embryotoxins, which require maternal metabolic activation, and for understanding the mechanisms of their metabolic activations.
Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan. miyata@mail.pharm.tohoku.ac.jp
Masaaki
M
Miyata
Etsuko
E
Tamura
Yasushi
Y
Yamazoe
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000633:toxicity; D001681:Biological Assay / Q000379:methods* / Q000706:statistics & numerical data; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011817:Rabbits; D013723:Teratogens / Q000378:metabolism* / Q000494:pharmacology*; D013792:Thalidomide / Q000378:metabolism / Q000633:toxicity
D013723:Teratogens; D001564:Benzo(a)pyrene; D013792:Thalidomide