Occurrence of induced 6-thioguanine-resistant colonies in synchronized V79 cells after treatment with ftorafur. Effects of the S9 fraction.

The capacity of ftorafur to induce resistance to 6-thioguanine in V79 hamster cells was investigated. The treatment conditions were arranged in order to favor the induction of such gene mutations. The synchronous cells were treated in the beginning of S phase, i.e., when the replication of the genes responsible for the expression of resistance to 6-thioguanine took place. Part of the experiments was carried out in presence of the S9 microsomal fraction. The results showed that ftorafur was a weak mutagen after a short-term exposure in the presence of adequate amounts of the S9 fraction. In absence of the S9 fraction or when other than-optimal amounts were used, we repeatedly failed to detect any increase in the occurrence of mutated cells. Also the cytotoxic effects of this substance were investigated. We found that a short-term treatment of V79 hamster cells with lower concentrations of ftorafur resulted in decrease of growth rate, higher concentrations after a short-term treatment were in turn slightly toxic. Long-term treatments are, depending on the concentration and time of treatment used, considerably toxic.