Initiation of carcinogenesis dependence upon MNNG-induced release of the G1 block of density-inhibited Syrian hamster cells.

After N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) treatment of density-inhibited postconfluent (DDIR) Syrian hamster embryo cell cultures, only a small population of the cells incorporate [3H]-thymidine within the next 10-20 h. The transformed colonies, observed subsequent to reseeding, are derived from the population incorporating [3H]-thymidine. This study demonstrates that MNNG-induced thymidine incorporation resulted from semiconservative DNA synthesis as analyzed by DNA density gradients. Furthermore, cell cycle distributions at selected times after treatment indicate that the MNNG-responsive population was released from the density-dependent G1 block, proceeded through S, and became blocked again at G2 or M. These results indicate that DNA synthesis is temporally related to an early step in carcinogenesis.