1. Nonlethal G0-ts mutant tsJT60 becomes lethal at the nonpermissive temperature after transformation: a hint for new cancer chemotherapeutics
- Author
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Jun Ninomiya-Tsuji, Masashi Shibuya, Kazuko Shiroki, Nobuo Tsuchida, Toshinori Ide, Naoko Ogawa, Sadahiko Ishibashi, Kiyomi Furuoku, Yang Yu Tai, and Kaoru Segawa
- Subjects
Methylnitronitrosoguanidine ,Cell division ,Physiology ,Antigens, Polyomavirus Transforming ,Recombinant Fusion Proteins ,Mutant ,Genes, myc ,Antineoplastic Agents ,Biology ,medicine.disease_cause ,Resting Phase, Cell Cycle ,Cell Line ,Antigen ,medicine ,Animals ,Molecular Biology ,Cell Line, Transformed ,Genetics ,Mutation ,Cell growth ,Adenovirus Early Proteins ,Temperature ,Cell Biology ,General Medicine ,Oncogene Proteins, Viral ,Oncogenes ,Cell cycle ,Cell Transformation, Viral ,Molecular biology ,Rats, Inbred F344 ,Rats ,Transformation (genetics) ,Cell Transformation, Neoplastic ,Genes, ras ,Cell culture ,Drug Design ,Carcinogens ,Genes, Lethal ,Oncogenic Viruses ,Cell Division - 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 degrees C. However, most of these clones grew slowly at 40 degrees C, producing many floating dead cells, and some clones were killed at 40 degrees 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 degrees 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 degrees 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.
- Published
- 1990