Chromosome instability in the murine melanoma cell line K-1735 is due to drug-specific mechanisms

The purpose of the present study was to investigate chromosomal instability and DNA repair by exposing clones from the murine melanoma cell line K-1735 to the radiomimetic drug bleomycin and to the DNA polymerase a inhibitor aphidicolin. Results from previous experiments conducted with human lymphocytes have suggested synergistic chromosomal damage after simultaneous exposure to these two agents. However, in the murine cell line studied here, there was no direct correlation between the effects of these two agents. Indeed, the extensive variation in the responses to aphidicolin and bleomycin suggested different mechanisms for the repair of bleomycin-induced DNA damage by the clones. Evaluation of the unexplained propensity of some bleomycin-treated metaphase cells to disintegrate suggested that this phenomenon was most likely the result of a direct action of bleomycin, rather than a potential manifestation of tumor cell instability.