Induction of retrovirus gene expression in mouse cells by some chemical mutagens

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 greater than 90% of AKR cells at a concentration of 2 to 4 micrograms/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.