Fidelity levels of DNA polymerases in tumorigenic state cells and serially transplantable tumor cells.
It is well known that point mutations exist in oncogenes and tumor suppressor genes of tumor cells, and one of the causes of these mutations may be misincorporation by error-prone DNA polymerases. This hypothesis is supported by the observation of decreased fidelity levels of DNA polymerases in mouse spleen containing tumorigenic cells after infection with Friend virus, and in aged animals that suffer high rates of tumorigenesis. However, this decrease in fidelity is disadvantageous for tumor cells maintained by serial transplantation. Therefore, we measured the fidelity levels of DNA polymerases in tumor cells transplanted through many passages. The fidelity levels of DNA polymerases from Yoshida ascites hepatoma, Rhodamine sarcoma, mouse ascites hepatoma-134, and Ehrlich ascites carcinoma cells derived from rats and mice are very high for in-vitro DNA synthesis on synthetic polynucleotides. These results suggest that many kinds of mutant cells arise during tumorigenesis. Among these mutant cells, cells showing decreased DNA polymerase(s) fidelities are present and these cells may undergo cell death. On the other hand, cells with mutations in various oncogenes and tumor suppressor genes and without mutations in DNA polymerase genes may survive as serially transplantable tumor cells.
Taguchi
T
T
Department of Molecular Biology, Tokyo Metropolitan Institute of Gerontology, Japan.
Fukuda
M
M
Ohashi
M
M
D000818:Animals; D002478:Cells, Cultured; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D051381:Rats; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured
D004259:DNA-Directed DNA Polymerase