Short-term cytogenetic assays of nine cancer chemotherapeutic drugs with metabolic activation.

Nine anticancer drugs were analyzed in cell cultures with respect to their cytogenetic effects with or without the addition of liver fraction S9 as an in vitro metabolic system. Among them, vincristine was the only drug which induced a significant accumulation of mitosis with or without S9. Adriamycin and neocarzinostatin were most potent in induction of chromosome breakage, but their clastogenic activities were reduced after metabolic conversion. On the other hand, cyclophosphamide had a dose-dependent activation of clastogenic effect by S9. The activity of bleomycin was enhanced by S9. S9 had no effect on the activities of actinomycin D, cytosine arabinoside, mitomycin C, and methotrexate. Vincristine showed no clastogenic property in our short-term assay system with or without S9. The activities of these anticancer drugs observed from our assay were compatible with those from other assay systems. The incorporation of S9 or other metabolic systems in routine clastogen assays should allow us to improve our understanding of the genetic toxicity of chemical agents.