Differential effects of cordycepin on the induction of sister-chromatid exchange and chromatid breaks in BALB/Mo mouse lymphocytes treated with mitomycin C.
BALB/Mo mice lymphocytes, carrying endogenous Moloney murine leukaemia virus (M-MuLV), show significantly higher in vitro baseline frequencies of sister chromatid exchange (SCE) than lymphocytes from control (M-MuLV free) BALB/c mice. In vitro treatment of lymphocytes with cordycepin (10 micrograms/ml), an antiviral substance, lowers the level of SCE in BALB/Mo cells to the same value of BALB/c cells. The drug also reduces the higher sensitivity of BALB/Mo compared to BALB/c lymphocytes to the induction of SCE by mitomycin C (MMC) administered either in vitro (3 x 10(-8), 10(-7) M) or in vivo (0.3, 3 mg/kg). BALB/Mo lymphocytes treated in vivo with a high dose of MMC (10 mg/kg) show reduced susceptibility to the induction of SCE but increased frequencies of chromatid breaks and micronuclei. In this situation, cordycepin increases the level of SCE in BALB/Mo lymphocytes to exactly the level seen in BALB/c cells, but it does not affect the frequency of chromosomal aberrations. Since cordycepin is known to inhibit poly(A) synthesis, thus blocking RNA maturation, it is suggested that M-MuLV proviral integration is not the sole factor responsible for the altered susceptibility of BALB/Mo lymphocytes to SCE induction, but that it is most likely viral gene expression that is needed for this effect to occur. On the contrary, the high susceptibility of BALB/Mo lymphocytes to the induction of chromatid aberrations by a high dose of MMC administered in vivo seems to be independent of viral maturation.
D000818:Animals; D002842:Chromatids / Q000187:drug effects* / Q000648:ultrastructure; D003839:Deoxyadenosines / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology*; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects
D003839:Deoxyadenosines; D008937:Mitomycins; D016685:Mitomycin