Dose response and growth rates of subcutaneous tumors induced with 3-methylcholanthrene in mice and timing of tumor origin.

The dose response of tumor induction after single s.c. injections of 3-methylcholanthrene (MC) into the groin of mice and the growth rates of the tumors formed were examined. The dose-response curve of tumor induction appeared to be linear at low doses of MC. Analysis of 182 sarcomas produced between 50 and 400 days after MC injection into WB and C3H/He mice, together with previous data on ICR/JCL mice, showed that there was no correlation between the volume-doubling time of tumors and the length of time before tumor appearance or the dose of carcinogen applied. The overall average volume-doubling time of sarcomas in the three strains of mice was 2.6 days. Assuming that a tumor originates from a single cell and that its growth rate before its appearance is constant, individual growth curves were extrapolated to the time of origin of each tumor. Histograms of the distribution of times of origin of tumors showed peaks at about 50 days after application of carcinogen. A one-hit and possibly two-stage type of tumor induction with MC is proposed.