Embryotoxicity induced by alkylating agents. Teratogenicity of acetoxymethyl-methylnitrosamine: dose-response relationship, application route dependency and phase specificity

Abstract

Acetoxymethyl-methylnitrosamine, the acetate ester of the presumed reactive metabolite of dimethylnitrosamine, is an effective teratogen in NMRI mice. An unusual phenomenon of application route specificity and a pronounced phase specificity of the teratogenic effects induced are demonstrated. Dose-response relationships are established. Some further arguments are given to support the basic hypothesis that the teratogenicity of alkylating agents is closely correlated to the DNA alkylation rate of embryonic cells.