Differential cell cycle phase specificity for neoplastic transformation and mutation to ouabain resistance induced by N-methyl-N'-nitro-N-nitrosoguanidine in synchronized C3H10T 1/2 C18 cells.
The transformable mouse embryo fibroblast cell line C3H10T 1/2 C18 has been employed to study the induction by the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) of morphological transformation and mutation to ouabain resistance throughout the cell cycle. Cells were synchronized by means of isoleucine deprivation for 24 hr and initiated DNA synthesis with a high degree of synchrony 7.5 hr after release of the isoleucine block. At various intervals throughout the cell cycle cultures were treated with MNNG at 1.0 microgram/ml and the induction of cytotoxicity, morphological transformation, and ouabain-resistant colonies was determined. All three phenomena exhibited marked cell-cycle phase dependency. Maximal induction of transformation occurred in cultured treated 7.5 hr after release from isoleucine deprivation, when the cells were at the G1/S boundary. In contrast, induction of ouabain-resistant colonies was at a minimum at the time of maximal induction of transformation, and peak induction of ouabain resistance did not occur until 16-18 hr after release from the isoleucine block, when cells were in late S phase. A close correlation was observed between the induction of cytotoxicity and of ouabain-resistant mutants. The results suggest that differences exist in the production or cellular processing of the various early lesions.
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004351:Drug Resistance; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology*; D051379:Mice; D009154:Mutation / Q000187:drug effects*; D010042:Ouabain / Q000494:pharmacology; D013997:Time Factors
D008769:Methylnitronitrosoguanidine; D010042:Ouabain