Embryotoxicity induced by alkylating agents: 8. DNA adduct formation induced by ethylmethanesulfonate in mouse embryos

Abstract

In previous studies using methylating agents a correlation was found between the initial DNA adduct rate (O⁶‐methylguanine) in the embryo and the teratogenic efficiency. This was shown by measuring DNA adduct rates in the teratogenic dose range which exhibited similar adduct rates at the equivalent teratogenic dose levels. A similar approach was performed using the ethylating agent ethylmethanesulfonate (EMS). In the teratogenic dose range (150–250 mg/kg bw) the adduct rates of O⁶‐ethylguanine were similar compared to those of O⁶‐methylguanine which were obtained with methylating agents. We conclude that a correlation between teratogenicity and adduct rate (O⁶‐alkylguanine) exists for both methylating and ethylating agents. Furthermore, DNA adduct formation following doses at and below the no‐observed‐adverse‐effect‐level (NOAEL) of teratogenicity was determined. The lowest experimental dose was 45 mg/kg EMS. Substantial DNA adduct rates in the embryos were found. These data will be used for molecular dosimetry in a risk assessment of low doses.