Sister chromatid exchanges and chromosomal aberrations induced by mitomycin C in mouse lymphocytes carrying a leukemogenic virus.
The induction of chromosomal damage (sister chromatid exchanges (SCEs), chromosomal aberrations, and micronuclei) in T lymphocytes from mouse spleen was analyzed after treatment in vivo with different concentrations of mitomycin C (MMC). Lymphocytes were derived from BALB/Mo mice, which carry an endogenous type C retrovirus (Moloney murine leukemia virus, M-MuLV), and from BALB/c mice (controls, M-MuLV-free). Chromosomal damage was determined in vitro on lymphocytes stimulated with concanavalin A (Con A) and incubated for two generation cycles with bromodeoxyuridine (BUdR). The baseline frequency of SCEs was significantly higher in untreated BALB/Mo than in BALB/c lymphocytes. The frequencies of SCEs were significantly increased by increasing doses of MMC in both BALB/c and BALB/Mo T lymphocytes. Treatment with a low dose of MMC (0.3 mg/kg) produced an additive effect on SCE frequency in BALB/Mo lymphocytes, which was gradually suppressed by increasing the MMC concentration (3-5 mg/kg). Indeed, the levels of SCEs became significantly lower in BALB/Mo than in BALB/c lymphocytes at the highest MMC concentration tested (10 mg/kg), indicating that a negative synergistic effect was eventually produced. Chromosomal aberrations (breaks and total aberrations) were significantly increased by the highest MMC doses (5-10 mg/kg) and were more frequent in BALB/Mo than in BALB/c lymphocytes at 10 mg/kg MMC. The frequencies of micronuclei were increased by all MMC doses and were significantly higher in BALB/Mo than in BALB/c lymphocytes at 10 mg/kg MMC. These results are referred to interferences of M-MuLV and MMC with the function of enzymes, such as DNA topoisomerases, involved in the mechanism of SCE production.
D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects; D002869:Chromosome Aberrations; D003434:Crossing Over, Genetic / Q000187:drug effects*; D007942:Leukemia, Experimental; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D016685:Mitomycin; D008937:Mitomycins / Q000633:toxicity*; D008979:Moloney murine leukemia virus; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000648:ultrastructure
D008937:Mitomycins; D016685:Mitomycin