Inhibition of recovery from potentially lethal damage by chemicals in Chinese hamster V79 A cells.

The inhibition of recovery from potentially lethal damage and the influence of mutation induction by lactate, pyruvate, novobiocin, and nalidixic acid was studied in the stationary phase of Chinese hamster V79 A cells. Lactate and pyruvate were selected to elucidate their possible involvement in the inhibition of recovery from PLD since high levels of lactate and pyruvate accumulate due to increased aerobic and anaerobic glycolysis in tumours. Effects of novobiocin and nalidixic acid were also studied to elucidate the possible role of an enzyme similar to DNA gyrase in the potentially lethal damage recovery of V79 cells. The inhibition of recovery depends on drug concentration and is complete with 20 mM of lactate and pyruvate and 20 microM of nalidixic acid and novobiocin. The chemicals seem to interfere with an early step in the recovery process. Incubation with novobiocin in a post-irradiation period does not change the mutation frequency significantly whereas lactate and pyruvate demonstrate a slight increase. Cells incubated with nalidixic acid showed a significant increase in mutation frequency at 24 h post-irradiation recovery time.