Formation of N-7-(2-carbamoyl-2-hydroxyethyl)guanine in DNA of the mouse and the rat following intraperitoneal administration of [14C]acrylamide.

Abstract:

:Acrylamide is an alkylating agent which reacts very slowly in direct reactions with DNA and is negative in the Ames test, but is carcinogenic in mice and rats. In order to explain the cancer-initiating properties of acrylamide we have studied DNA adduct formation in vitro with a metabolizing system and in vivo in mice and rats following i.p. administration of 14C-labeled acrylamide. A major adduct found in both species was N-7-(2-carbamoyl-2-hydroxy-ethyl)guanine, formed by reaction of 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 distributed among tissues and that the organ-specificity in acrylamide carcinogenesis cannot be explained by a selective accumulation of the DNA-reactive metabolite in target organs.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Segerbäck D,Calleman CJ,Schroeder JL,Costa LG,Faustman EM

doi

10.1093/carcin/16.5.1161

subject

Has Abstract

pub_date

1995-05-01 00:00:00

pages

1161-5

issue

5

eissn

0143-3334

issn

1460-2180

journal_volume

16

pub_type

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