DNA Repair Pathways in Mammalian Cells Analyzed by Isolation of ACNU-Sensitive Chinese Hamster Ovary Cells

Masayuki Numata, Hiroaki Hata, Hiroko Tohda, Akira Yasui, Atsushi Oikawa

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    1 Citation (Scopus)

    Abstract

    1-[(4-amino-2-metliyl-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.

    Original languageEnglish
    Pages (from-to)123-128
    Number of pages6
    JournalTohoku Journal of Experimental Medicine
    Volume168
    Issue number2
    DOIs
    Publication statusPublished - 1992

    Keywords

    • ACNU
    • CHO mutant
    • DNA repair
    • chloroethylating agent
    • cross linking

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)

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