FORMATION OF N-7-(2-CARBAMOYL-2-HYDROXYETHYL)GUANINE IN DNA OF THE MOUSE AND THE RAT FOLLOWING INTRAPERITONEAL ADMINISTRATION OF [C-14] ACRYLAMIDE

Acrylamide is an alkylating agent which reacts very slowly in direct r eactions with DNA and is negative in the Ames test, but is carcinogeni c in mice and rats. In order to explain the cancer-initiating properti es of acrylamide we have studied DNA adduct formation in vitro with a metabolizing system and in vivo in mice and rats following i.p. admini stration of C-14-labeled acrylamide. A major adduct found in both spec ies was N-7-(2- carbamoyl-2-hydroxyethyl)guanine, formed by reaction o f the DNA with the epoxide metabolite glycidamide. The levels of this adduct were similar in the different organs of the two rodent species, which supports the notion that glycidamide is relatively evenly distr ibuted among tissues and that the organ-specificity in acrylamide carc inogenesis cannot be explained by a selective accumulation of the DNA- reactive metabolite in target organs.