Molecular mechanism of in vitro transformation of mammalian cells by chemical carcinogens.

BHK21 clone 13 cells transformed by dimethylnitrosamine (DMN) or nitrosomethylurea (NMU) ("alkylating" chemical carcinogens) appear to be restricted by temperature in the expression of their transformed phenotype. When grown at 38.5 degrees C, they exhibit a transformed phenotype (clonal morphology and ability to plate in agar), when grown at 32 degrees C, their phenotype is normal. Conversion from the normal to the transformed phenotype and the reverse is possible by temperature shifts. Conversely of the BHK21 clone 13 cells, of the rat fibroblasts (R111) transformed by 4-nitroquinoline-N-oxide (NQN), some exhibit a transformed phenotype restricted by temperature while others are not restricted by temperature in the expression of transformation. A working hypothesis is proposed suggesting that the phenotype of cells transformed by chemical carcinogens may be determined by the nature of the chemical reaction with the cell DNA. "Alkylating" carcinogens cause prevalently point mutation in bacteria (of the base substitution kind); in the case of transformation of mammalian cells temperature-sensitive phenotypes will be obtained. "Frameshift" carcinogens cause frameshift mutation in bacteria and cells transformed by this class of carcinogens will exhibit a transformed phenotype unrestricted by temperature.