Embryotoxicity induced by alkylating agents: 8. DNA adduct formation induced by ethylmethanesulfonate in mouse embryos.
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.
Platzek
T
T
Institut für Toxikologie und Embryopharmakologie, Freie Universität Berlin, Germany.
Bochert
G
G
Rahm
U
U
D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D004247:DNA / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000187:drug effects*; D005020:Ethyl Methanesulfonate / Q000633:toxicity*; D005260:Female; D005865:Gestational Age; D051379:Mice; D011247:Pregnancy; D013723:Teratogens / Q000633:toxicity*
D000477:Alkylating Agents; D013723:Teratogens; D004247:DNA; D005020:Ethyl Methanesulfonate