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.