Comparison of the Relative Mutagenic Activity for Eight Antineoplastic Drugs in the Ames Salmonella/Microsome and TK+/− Mouse Lymphoma Assays

Abstract

Eight antineoplastic drugs were evaluated for their ability to induce mutation in the Ames Salmonella/microsome and the TK+/- mouse lymphoma assay. Dose response data were utilized to determine the relative potency of each of these drugs. They were then ranked based on this information. Vincristine, the most potent compound tested in the mouse lymphoma assay, was not active in the Salmonella assay, nor were DTIC and Methotrexate. Excluding these compounds from the comparison ranking, we found that the only difference in the order between the Ames and lymphoma assays was between Daunomycin and Adriamycin. Daunomycin was most potent in the Ames assay, compounds was reversed in the mouse lymphoma assay. This observation of relative activity is of interest because it underscores the ability to extrapolate between microbial and mammalian test systems, provided one keeps in mind the differences associated with chromosome structure and modes of segregation in these two cell types. Furthermore, it is suggested that relative potency ranking may provide prospective insight into expectations of risk for human populations exposed to these drugs.