Absence of genotoxic effects in cells exposed to four ketonucleoside derivatives

The relationship between the structure and genotoxic potential of four new cytostatic compounds--the ketonucleosides KN-35, KN-43, KN-44 and KN-3--was investigated in short-term in vitro assays of hypoxanthine-guanine phosphoribosyl transferase locus mutation in V79 cells, induction of chromosomal aberrations and sister chromatid exchanges on human lymphocytes, induction of chromosomal aberrations and micronuclei in V79 cells, and transformation of Syrian hamster embryo cells. None of the ketonucleosides induced mutagenic effects in any of the assays. Their failure to exhibit significantly genotoxic activity may be ascribed to the probable absence of any reaction between these drugs and the cellular DNA, and indicates that they act by some other mechanism which probably differs from the one observed with alkylating or intercalating antitumoural agents. This suggests that the cytotoxic activity of ketonucleosides cannot be related to genotoxicity.