Embryotoxicity induced by alkylating agents: 8. DNA adduct formation induced by ethylmethanesulfonate in mouse embryos
- 1 January 1994
- journal article
- Published by Wiley in Teratogenesis, Carcinogenesis, and Mutagenesis
- Vol. 14 (2) , 65-73
- https://doi.org/10.1002/tcm.1770140203
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.Keywords
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