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DNA repair pathways in mammalian cells analyzed by isolation of ACNU-sensitive Chinese hamster ovary cells
- Source :
- The Tohoku journal of experimental medicine. 168(2)
- Publication Year :
- 1992
-
Abstract
- NUMATA, M., HATA, H., TOHDA, H., YASUI, A and OIKAWA, A. DNA Repair Pathways in Mammalian Cells Analyzed by Isolation of ACNU-Sensitive Chinese Hamster Ovary Cells. Tohoku J. Exp. Med., 1992, 168 (2), 123-128 - 1-[(4- amino-2-methyl-5-pyrimidinyl)methyl]-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) causes chloroethylation of DNA strand followed by cross linking through an ethylene bridge. We recently isolated two ACNU sensitive mutants from mutagenized Chinese hamster ovary cells, and found them to be new drug sensitive recessive mutansts (Hata et al. 1991). The O6-methyl guanine DNA methyl transferase (MT) activities of these cells were undetectable as the parental cell line, indicating that the sensitivity of the mutant cell lines to ACNU was not due to the decreased cellular level of this enzyme. By complementation analysis with the 7 established UV-sensitive CHO cell lines, one of the mutants, UVS1, turned out to complement their UV-sensitivity and, therefore, build a new complementation group among all the CHO cell lines ever reported. The other mutant, CNU1 showed hypersensitivity only to chloroethylating agents (ACNU, CCNU) and exhibited a slightly reduced unscheduled DNA synthesis (UDS) induced by UV. It is, therefore, suggestive that this mutant is defective in a specific step of DNA repair systems, which is important for the processing of DNA damages produced by ACNU. Only cell lines from the complementation group 1 and 4 out of 7 established complementation groups of UV-sensitive CHO mutants were more sensitive to ACNU than UVS1 and CNU1, indicating some steps of excision repair pathways as well as specific repair system play important roles in repairing ACNU-induced DNA damages. - chloroethylating agent; ACNU; cross linking; DNA repair; CHO mutant
- Subjects :
- DNA Repair
DNA repair
Guanine
Ultraviolet Rays
Chinese hamster ovary cell
Mutant
General Medicine
CHO Cells
Cell Separation
Biology
Molecular biology
General Biochemistry, Genetics and Molecular Biology
Complementation
chemistry.chemical_compound
Nimustine
chemistry
Cell culture
Cricetinae
Mutation
Animals
Drug Screening Assays, Antitumor
DNA
Nucleotide excision repair
Subjects
Details
- ISSN :
- 00408727
- Volume :
- 168
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- The Tohoku journal of experimental medicine
- Accession number :
- edsair.doi.dedup.....7a380450b9dd8848a13b74fe24212fe8