Possible repair of carcinogenic damage caused by dimethylnitrosamine in rat kidney

Abstract

SINCE the discovery that cells from patients with xeroderma pigmentosum, a disease associated with a high incidence of cancer, may be unable to excise ultraviolet light-induced thymine dimers from DNA¹, and the recognition of the possibility that all carcinogens react with the DNA of the organs in which tumours are induced², it has been thought that repair of changes produced in DNA by carcinogens might be important in moderating the effectiveness of these compounds. Work on the carcinogenic effect of prolonged administration of various chemicals³, however, suggests that individual carcinogenic doses are entirely cumulative in their action, and that the carcinogenic damage is permanent and not repaired⁴. If this were correct, repair of lesions produced in DNA by carcinogens would seem to have no direct relevance to carcinogenesis. Recovery from the lethal effects of radiation was established by the classic experiments of Elkind and Sutton⁵ in which cultured cells were irradiated twice with different intervals between the first and second dose; if sufficient time elapsed between the first and second dose, the effects of the doses were not cumulative. We have used an analogous experimental design to study the cumulation of the effect of dimethylnitrosamine in the induction of kidney tumours in the rat. The experiment is not yet complete, but we believe we have demonstrated that a repair process exists.