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Induction of Retrovirus Gene Expression in Mouse Cells by Some Chemical Mutagens¹

Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37830

Cell cultures derived from a variety of mouse strains were compared for their relative capacity to be induced to express endogenous retrovirus proteins by exposure to 5-iododeoxyuridine under optimized experimental conditions. Induction frequencies varied between 6.0 x 10^–1 and 1.7 x 10^–2 with AKR cells showing the highest capacity and C57BL/6 x C3H F₁ cells the lowest. Virus expression was induced in AKR cells with other chemical mutagens of the polyaromatic hydrocarbon [benzo(a)pyrene and phenol, diol, and epoxide metabolites] and nucleoside analog classes, but alkylating agents were inconsistent or failed to induce. Considerable differences in the efficiency of induction were seen between various halogenated nucleosides, while under these conditions the nucleoside 5-azacytidine induced >90% of AKR cells at a concentration of 2 to 4 µg/ml. The high frequency of induction by 5-azacytidine, relative to other nucleoside analogs, and the absence of induction by other mutagens further indicate that endogenous virus induction occurs via nonmutagenic mechanisms and that some mutagens may also affect regulatory functions independent of their mutagenic action.

¹ Research sponsored jointly by the Office of Research and Development, Environmental Protection Agency, under Interagency Agreement (EPA-81-D-KO533) and the Office of Health and Environmental Research, United States Department of Energy, under Contract W-7405-eng-26 with the Union Carbide Corporation.

² To whom requests for reprints should be addressed. Present address: Cellular and Genetic Toxicology Branch, National Institute of Environmental Health Sciences, P. O. Box 12233, Research Triangle Park, N. C. 27709.

³ Present address: Department of Biological Sciences, Illinois State University, Normal, Ill. 61761.

Received 12/ 4/81. Accepted 5/ 6/82.