Lack of genotoxic and cytotoxic effects of the herbicide lenacil on mouse tumor cells and on some Salmonella typhimurium strains.

The effects of 3-cyclohexyl-6,7-dihydro-1H-cyclopentapyrimidine-2,4(3H,5H)-dione (lenacil) on macromolecular synthesis, thymidilate synthetase activity, viability and cell cycle progression were studied using Friend leukemia (FL). P388 and Ehrlich ascites tumor cells in suspension, and its cytogenetic effects were studied in a Salmonella/mammalian microsome assay using both frameshift and base-substitution tester strains. At a concentration of 0.5 mmol/l lenacil inhibited 45 to 70% thymidine incorporation into DNA fraction, while incorporations of uridine into RNA and leucine into protein were less affected. Thymidilate synthetase activity in P388 cells as assayed by the release of tritiated water from 5-3H-deoxyuridine was inhibited by the compound to about 20%. Lenacil neither showed an in vivo inhibitory action on thymidine incorporation into acid-insoluble material in P388 cells, nor on thymidilate synthetase activity after a 24 or 48 h treatment. The compound did not change the melting temperature of isolated DNA. Studies of lenacil's effect on cell cycle kinetics of FL cells demonstrated that 48 h treatment increased the percentage of S-phase cells. Lenacil exerted a weak cytotoxic effect on FL cells. At concentrations above 0.1 mmol/l it inhibited cell growth the effect being nonlethal. Cytogenetic studies of lenacil revealed no indication of its mutagenicity against Salmonella typhimurium TA97, TA98, TA100 and TA102.