Nonlethal G₀-ts mutant tsJT60 becomes lethal at the nonpermissive temperature after transformation: A hint for new cancer chemotherapeutics⁶

Abstract

tsJT60 is a nonlethal temperature-sensitive (ts) mutant of a Fischer rat cell line (3Y1) classified as a G₀ mutant; i.e., the ts defect is not expressed within the cell growth cycle but is expressed only between the G₀ and S phase. tsJT60 clones transformed with oncogenes such as adenovirus E1A, polyoma large T, polyoma middle T, v-Ki-ras, and LTR activated c-myc, or with a chemical carcinogen N-methyl-N'-nitro-N-nitrosoguanidine, grew well at 34°C. However, most of these clones grew slowly at 40°C, producing many floating dead cells, and some clones were killed at 40°C. When they were cultured under conditions inadequate for growth of untransformed cells, such as high cell density or serum restriction, they were killed at 40°C. These and previous results from SV40- and adenovirus-transformed tsJT60 clones favour the idea that transformed tsJT60 cells occasionally enter the G₀ phase and are metabolically imbalanced at 40°C during self-stimulation from the G₀ to S phase. We propose that a drug which exclusively block, G₀-G₁ transition would be cytocidal to transformed cells but cytostatic to normal cells.