Sister chromatid exchanges induced in vivo and in vitro by chemical carcinogens in mouse lymphocytes carrying endogenized Moloney leukemia virus

The induction of sister chromatid exchanges (SCEs) was analysed in mouse spleen T lymphocytes treated in vivo or in vitro with chemical carcinogens. Lymphocytes were obtained from BALB/Mo mice, which carry the Moloney murine leukemia virus (M-MuLV) as endogenous type C retrovirus, and from control BALB/c mice (M-MuLV free). SCEs were determined in vitro on lymphocytes stimulated with con-canavalin A (Con A) and incubated for two generation cycles with bromodeoxyuridine (BUdR). The baseline frequency of SCEs in untreated lymphocytes obtained from 2–3 month old and 4 day old BALB/Mo mice was significantly higher when compared with that observed in control BALB/c lymphocytes. Treatments in vitro with 10−6 M hexavalent chromium (Cr(VI)( as potassium dichromate) and 10−7 M, or 3 × 10−7 M mitomycin C (MMC) increased the SCE frequency in BALB/c lymphocytes, even more in BALB/Mo lymphocytes, indicating that M-MuLV and chemical carcinogens interacted synergistically in inducing SCEs in the presence of BUdR. On the other hand, the frequencies of SCEs in either BALB/c or BALB/Mo lymphocytes were not modified by treatment in vitro with 10−3 M trivalent chromium (Cr(III), as chromium chloride), which is genetically inactive. Treatment in vivo with 0.3 mg/kg MMC or 1 mg/g urethane followed by incubation in vitro with BUdR in the absence of the carcinogens produced only additive effects on BALB/Mo lymphocytes. The same was observed when unstimulated BALB/Mo lymphocytes were treated in vitro with MMC in the absence of BUdR, and then stimulated and incubated with BUdR but not with MMC. Treatment in vivo with a high dose of MMC (10 mg/kg), produced negative synergistic effects on the induction of SCEs in BALB/Mo lymphocytes. The different interaction of M-MuLV and chemicals on the induction of SCEs was interpreted in terms of positive or negative interference of the oncogenic virus and chemical carcinogens with the functions of enzymes, such as DNA topoisomerases, involved in the mechanism of SCE production, and was tentatively ascribed to the presence of larger DNA replicons in BALB/Mo than in BALB/c lymphocytes.