Repair of sub-lethal damage and unscheduled DNA synthesis in mammalian cells treated with monofunctional alkylating agents.

Abstract

THE cell cycle of exponentially growing mammalian cells is arbitrarily divided into four phases1. During the S phase, the cells replicate their DNA in preparation for mitosis, but Rasmussen and Painter2 and later others3,4 have shown that ultraviolet and X-irradiation can cause cells in other phases of the cell cycle to initiate DNA synthesis. Such unscheduled DNA synthesis is non-conservative, as shown by density gradient experiments3,5. Because of the similarity between this and repair synthesis in bacteria after ultraviolet radiation (and also because of the reduced unscheduled synthesis in cells from patients suffering from the hereditary disease, xeroderma pig-mentosum, who are extremely sensitive to ultraviolet radiation5), unscheduled and repair syntheses have been equated. After ultraviolet radiation, however, repair of sub-lethal damage (measured by increased survival in split dose experiments) is not observed6 nor, at least in some cell lines, is the excision of thymine dimers7. The large doses of X-irradiation required to give a measurable amount of unscheduled DNA synthesis made correlation with survival difficult. For these reasons, some question has remained about the biological function of unscheduled DNA synthesis.