DEMONSTRATION OF INVIVO DNA-REPAIR SYNTHESIS IN MOUSE SKIN EXPOSED TO VARIOUS CHEMICAL CARCINOGENS

Abstract

Chemical carcinogen-induced unscheduled DNA synthesis in mouse skin in vivo was demonstrated with the aid of a mechanical device. An isotonic aqueous solution containing a carcinogen and [methyl-3H]thymidine was injected s.c. into an isolated portion of the skin clamped off with ring-shaped forceps. Dose-dependent unscheduled DNA synthesis was clearly demonstrated as silver grains on the nuclei of both epithelial and dermal fibroblastic cells in this portion of skin in response to treatment with methyl methanesulfonate, 1-methyl-1-nitrosourea, 4-nitroquinoline 1-oxide, and 4-hydroxyaminoquinoline 1-oxide. The range of variability was small among animals and within a single area of skin. This system should be useful for quantitative measurement of unscheduled DNA synthesis in individual cells of the skin in vivo. Unscheduled DNA synthesis in response to various carcinogens was 3- to 5-fold more active in epithelial cells than in dermal fibroblastic cells. A time course study showed that active unscheduled DNA synthesis could be detected after 10 min, implying that adduct removal with resulting synthesis had occurred by this time.