Embryotoxicity induced by alkylating agents: 1. Ethylmethanesulfonate as a teratogen in mice.

The directly acting monofunctional alkylating agent ethylmethanesulfonate is a potent teratogen in NMRI mice. Inspection of skeletal abnormalities revealed a clear-cut phase specificity of the teratogenic outcome, especially of the limb malformations, after single intraperitoneal injections on days 9, 10, 11 or 12 of pregnancy. Dose-response studies were performed using single i.p. treatment of day 11. A computer program was developed for probit transformation of the data and maximum-likelihood estimation of the dose-response curves, including standard deviations and comparison of the slopes. Some arguments are presented for the hypothesis that the teratogenicity of simple alkylating agents is quantitatively correlated to a well-defined DNA alkylation rate of embryonic cells at the O-guanine site. [ABSTRACT FROM AUTHOR]