This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hogy, L. L. Articles by Guengerich, F. P. Search for Related Content PubMed PubMed Citation Articles by Hogy, L. L. Articles by Guengerich, F. P.

In Vivo Interaction of Acrylonitrile and 2-Cyanoethylene Oxide with DNA in Rats¹

Departments of Pharmacology [L. L. H.] and Biochemistry [F. P. G.] and Center in Molecular Toxicology [L. L. H., F. P. G.], Vanderbilt University School of Medicine, Nashville, Tennessee 37232

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.

¹ Supported in part by USPHS Grants ES 02205 and ES 00267.

² Burroughs Wellcome Scholar in Toxicology (1983–1988). To whom requests for reprints should be addressed.

Received 12/10/85. Revised 4/14/86. Accepted 5/ 5/86.

This article has been cited by other articles:

				B. I. Ghanayem, A. Nyska, J. K. Haseman, and J. R. Bucher Acrylonitrile Is a Multisite Carcinogen in Male and Female B6C3F1 Mice Toxicol. Sci., July 1, 2002; 68(1): 59 - 68. [Abstract] [Full Text] [PDF]

				H. Zhang, L. M. Kamendulis, J. Jiang, Y. Xu, and J. E. Klaunig Acrylonitrile-induced morphological transformation in Syrian hamster embryo cells Carcinogenesis, April 1, 2000; 21(4): 727 - 733. [Abstract] [Full Text] [PDF]

				L.M. Kamendulis, J. Jiang, Y. Xu, and J.E. Klaunig Induction of oxidative stress and oxidative damage in rat glial cells by acrylonitrile Carcinogenesis, August 1, 1999; 20(8): 1555 - 1560. [Abstract] [Full Text] [PDF]

				B. I. Ghanayem, J. M. Sanders, B. Chanas, L. T. Burka, and F. J. Gonzalez Role of Cytochrome P-450 2E1 in Methacrylonitrile Metabolism and Disposition J. Pharmacol. Exp. Ther., May 1, 1999; 289(2): 1054 - 1059. [Abstract] [Full Text]