Relationships between ethylation of hemoglobin, ethylation of DNA and administered amount of ethyl methanesulfonate in the mouse.

Ethylation of guanine-N-7 in the DNA of liver and kidney and of nucleophilic groups in hemoglobin has been studied as a measure of the in vivo dose in the mouse after i.p. administration of radiolabeled ethyl methanesulfonate (EMS). The degree of ethylation in both hemoglobin and DNA of the studied tissues was found to increase proportionally to the injected amount in the range 0.32-100 mumoles EMS/kg b.w. Above this range a somewhat higher than proportional degree of ethylation was found, indicating saturation of a system for detoxification of the compound, resulting in a decreased rate of elimination and consequently an increased dose in the tissues of this directly alkylating agent. The ratio between covalent binding to DNA and to hemoglobin, however, was approximately constant over the wide range of doses studied. For biological effects with a linear dose-response relationship, this demonstrates the validity of hemoglobin alkylation as an indicator of the risk.