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Main Title Rat Conceptus Development in Vitro: Comparative Effects of Alkylating Agents.
Author Sanyal, M. K. ; Kitchin, K. T. ; Dixon, R. L. ;
CORP Author National Inst. of Environmental Health Sciences, Research Triangle Park, NC.;Health Effects Research Lab., Research Triangle Park, NC.
Year Published 1980
Report Number EPA-600/J-81-272;
Stock Number PB81-235780
Additional Subjects Toxicology ; Rats ; Laboratory animals ; In vitro analysis ; Culture media ; Reprints ; Alkylating agents ; Embryos ; Toxic substances
Library Call Number Additional Info Location Last
NTIS  PB81-235780 Some EPA libraries have a fiche copy filed under the call number shown. 07/26/2022
Collation 8p
Conceptuses removed from the rats in the eleventh day of gestation were cultured in vitro for 2 days. Growth and differentiation of the major organs of the embryo in vitro resembled those developed in vivo. Embryonic development and organogenesis were markedly affected when the alkylating agents TEM (2,4,6-triethylenimino-1,3,5-triazine) and nitrogen mustard (mechlorethamine hydrochloride) were added to the culture medium. At concentrations of 1 and 5 micrograms/ml medium, these teratogens were highly embryotoxic and affected both growth and differentiation. DNA and protein content of embryos and yolk sacs was reduced significantly (p<0.001) from the controls. Development of conceptuses in the culture medium that contained cyclophosphamide (0.35 mM) alone apparently were normal. However, addition of cyclophosphamide (0.35 mM), microsomes (0.5 mg protein/ml), and NADPH (1 mM) to the culture medium induced marked deleterious effects on the conceptus growth and defferentiation. DNA and protein contents were significantly (p>0.001) reduced by the combined treatment indicative of formation of reactive metabolites and their interaference with macromolecular biosynthesis. Aminopyrine which has not been shown to be teratogenic, in equimolar amounts to cyclophosphamide, under identical conditions of culture, did not affect conceptus development.