Alkylation of protein and DNA in mice treated with urethane.

14C-labelled urethane in the dose interval 1-260 mg/kg was given to male CBA mice by i.p. injection. The formation of epoxyethyl carbamate, the suggested electrophilic intermediate of urethane, was studied through measurements of 2-oxoethyl adducts to the amino acids cysteine, terminal valine and histidine in protein (especially haemoglobin) and to N-7 of guanine in DNA in various tissues 9 h after treatment. The extent of binding to haemoglobin and liver DNA increased linearly with administered amount, in accordance with a complete clearance of urethane at all doses. The DNA binding varied between organs and decreased in the order liver greater than kidney greater than spleen greater than testis.