| Abstract: | We examined the relationship of cytotoxicity, mutagenesis, and malignant transformation by measuring in parallel clonogenic survival, mutation to ouabain resistance, and malignant transformation in cultured C3H mouse 10T 1/2 cells. Exposure of caffeine alone for 48 hours was cytotoxic and induced transformation in a dose-dependent manner. However, this same treatment did not induce any detectable ouabain-resistant mutants. When caffeine was present for 48 hours immediately following UV irradiation, alkaline sucrose gradient sedimentation of DNA showed that postreplication repair was inhibited. This inhibition of repair was correlated with reduced survival and inhibition of mutation induction, but the transformation frequencies were either unaltered or potentiated, depending on the UV dose and caffeine concentration. Thus, these experiments demonstrate that gene mutation and malignant transformation in 10T 1/2 cells can be dissociated. We suggest that the mechanism of transformation of 10T 1/2 cells is nonmutagenic in nature. |
