Cycle-related toxicity and transformation in 10T1/2 cells treated with N-methyl-N'-nitro-N-nitrosoguanidine

Exposure of C3H 10T1/2 Cl 8 cells, synchronized by release from confluence-induced arest of proliferation, to different concentrations of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for 30 min at various points during the cell cycle causes dose-dependent toxicity (decrease in relative colony-forming efficiency or "survival") that increases linearly during the first G1 phase, reaches a maximum in early to middle S phase, and decreases during late S. In the course of the second S phase, toxicity again becomes maximal. The transformation rate (type III foci) increases and decreases with a similar pattern, increasing during the first G1 phase to a maximum during early S phase, subsequently decreasing, and then increasing again during the second S phase. Although periods of maximal toxicity and transformation roughly coincide with some portion of the S phase, the mechanisms underlying these phenomena appear to differ for the following reasons: (a) toxicity is linearly related to dose of MNNG, whereas the latter is linearly related to the logarithm of transformation rate, and (b) the ratio between toxicity and transformation varies with the cycle phase and the dose of MNNG.