An inhibitor of potentially lethal damage (PLD) repair reduces the frequency of gamma-ray-induced mutations in cultured Chinese hamster V79 cells.

Cordycepin (3'-deoxyadenosine, 3'-dA) is an RNA antimetabolite and a radiosensitizer in cultured mammalian cells. In the present paper, the effects of 3'-dA on gamma-ray-induced lethality and 6-thioguanine (6TG)-resistant mutations in cultured Chinese hamster V79 cells were examined. 3'-dA had the effect of sensitizing the lethality induced by gamma-rays. The potentially lethal damage (PLD) repair produced by post-incubation of cells in Hanks' solution after gamma-irradiation was almost completely suppressed by 5 x 10(-5) M 3'-dA. When cells were irradiated with 10 Gy gamma-rays and incubated with 3'-dA for 5 h, the frequency of 6TG-resistant mutations induced by gamma-rays decreased to one-sixth of that of irradiated cells incubated without 3'-dA. The decrease in the frequency of gamma-ray-induced mutations was dependent on the length of incubation time with 3'-dA. It is suggested that the inhibition of PLD repair by 3'-dA may be that of error-prone repair.