Several approaches were used to probe aspects of the mechanism of acrylonitrile carcinogenicity in rats. Acrylonitrile did not appear to increase the rate of DNA synthesis resulting from tissue injury and regeneration in liver or brain, the latter being a target organ. The chemical did cause unscheduled DNA synthesis in rat liver but not brain. The epoxide of acrylonitrile, 2-cyanoethylene oxide, was formed in perfused rat liver; this metabolite accumulated in the perfusate as long as acrylonitrile was available to the organ. When 2-cyano[2,3-14C]ethylene oxide was administered to rats i.p., covalent binding to both liver and brain protein was found, but no covalent binding to nucleic acids could be detected at the level of 0.3 alkylations per 106 bases. No 1,N6-ethenoadenosine or 1,N6-ethenodeoxyadenosine was found in liver nucleic acids after administration of either acrylonitrile or 2-cyanoethylene oxide to rats, with the limits of detection being 0.3 alkylations per 106 RNA bases and 1 alkylation per 106 DNA bases. However, low levels of N7-(2-oxoethyl)guanine were detected in the livers of these rats by means of a radiometric derivative assay (0.014–0.032 alkylations per 106 DNA bases). In the brains of the treated rats the levels of N7-(2-oxoethyl)guanine were not above the limit of detection. These results show that acrylonitrile has some limited potential for genotoxicity in vivo and that the epoxide, with its ability to leave the liver and possibly to enter the brain, can interact with nucleic acids to a limited degree.


Supported in part by USPHS Grants ES 02205 and ES 00267.

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