The role of cell division in the malignant transformation of mouse cells treated with 3-methylcholanthrene.

The requirement for cell division in the malignant transformation of A31-714 cells, a subclone derived from BALB/3T3, by 3-methylcholanthrene was investigated using the property of the high susceptibility of this clone to density-dependent inhibition of cell growth. Treatment with 3-methylcholanthrene did not induce transformation in a nongrowing population. However, the cells treated with the arcinogen in a nongrowing state showed a high transformation frequency near maximum level when they were returned to the growing state soon after treatment. About four cell generations were found to be necessary for the development of cell transformation after treatment with 3-methylcholanthrene. Cells that were kept in a nongrowing state after carcinogen treatment rapidly lost their ability to express transformation even when they were subsequently returned to a growing state. On the other hand, the cells that were allowed one cell division soon after carcinogen treatment retained their ability to produce transformed foci even after being kept in the nongrowing state thereafter. These results suggest that one cell generation is required for the fixation of transformation and that several additional cell generations are required for the expression of the transformed state.