Enhancement of radiosensitivity of cultured mammalian cells by neocarzinostatin. I. Inhibition of the repair of sublethal damage.

The enhancement of radiosensitivity by neocarzinostatin (NCS), an antitumour drug, was studied using three strains of cultured mammalian cells with different repair capabilities for sublethal damage. NCS enhanced the radiosensitivity of the cells when applied both during and after X-irradiation under aerobic conditions. The enhancement ratios of NCS during X-irradiation were 1.25, 1.27 and 1.38 for mouse lymphoma L5178Y, Chinese hamster V79 and mouse mammary tumour FM 3A cells, respectively. The corresponding ratios after X-irradiation were 1.18, 1.27 and 1.38, respectively. These ratios were proportional to the repair capabilities of the cells for sublethal damage. NCS completely inhibited the repair of sublethal damage regardless of the repair capabilities of the cells for sublethal damage. NCS was equally effective for hypoxic cells. These results suggested that NCS enhanced the radiosensitivity of the cells probably by interacting with the residual damage after X-irradiation, thereby converting the sublethal damage or potentially lethal damage into lethal damage.