Nonlethal G0-ts mutant tsJT60 becomes lethal at the nonpermissive temperature after transformation: a hint for new cancer chemotherapeutics.
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.
Tai
Y Y
YY
Department of Physiological Chemistry, Hiroshima University School of Medicine, Japan.
Ninomiya-Tsuji
J
J
Furuoku
K
K
Ogawa
N
N
Ishibashi
S
S
Shiroki
K
K
Segawa
K
K
Tsuchida
N
N
Shibuya
M
M
Ide
T
T
D017456:Adenovirus Early Proteins; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D002455:Cell Division; D002460:Cell Line; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics*; D002472:Cell Transformation, Viral; D015195:Drug Design; D005804:Genes, Lethal; D016259:Genes, myc; D011905:Genes, ras; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D009154:Mutation; D009856:Oncogene Proteins, Viral / Q000235:genetics; D009857:Oncogenes; D009858:Oncogenic Viruses / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000502:physiology; D016192:Resting Phase, Cell Cycle; D013696:Temperature
D017456:Adenovirus Early Proteins; D000952:Antigens, Polyomavirus Transforming; D000970:Antineoplastic Agents; D002273:Carcinogens; D009856:Oncogene Proteins, Viral; D011993:Recombinant Fusion Proteins; D008769:Methylnitronitrosoguanidine