The use of DNA-repair-deficient mutants of Chinese hamster ovary cells in studying mutagenesis mechanisms and testing for environmental mutagens

Journal Article · Sat Jan 01 04:00:00 EST 1983 · Basic Life Sci.; (United States)

DOI:https://doi.org/10.1007/978-1-4684-4382-0_9· OSTI ID:5894832

Thompson, L H

Our laboratory has taken a somatic-cell-genetics approach to the study of mutagenesis by utilizing mutant strains of Chinese hamster ovary (CHO) cells that are deficient in DNA repair processes. From more than 150 UV-sensitive strains tested, five complementation classes were identified, and representative mutants were found to be defective at, or before, the incision step of excision repair. A representative mutant, strain UV-5, was compared with the parental strain in terms of cytotoxicity and dose-response curves for mutation induction after treatment with UV and several chemicals that are known to produce large adducts in DNA. Excision repair in normal CHO cells protects against both cytotoxicity and mutagenesis, but the degree of protection depends on both the agent and the genetic marker used for detecting mutations. Upon treatment with low doses (100% cell survival) of the polyaromatic hydrocarbon, 7-bromomethylbenz(a)anthracene, repair-deficient UV-5 cells had linear responses for mutation induction to thioguanine resistance or azaadenine resistance, whereas the normal repair-proficient cells showed curvilinear responses in which the slope increased with dose. This behavior suggests that in the normal cells the repair system acting on potentially mutagenic lesions becomes saturated at doses that produce cytotoxicity. In no instance was a lower mutation frequency induced in UV-5 cells than the parental cells, at a given dose of mutagen, suggesting that the excision repair system is error-free in normal CHO cells.

• Research Organization: Biomedical Sciences Division, Lawrence Livermore National Laboratory, Livermore, CA
• OSTI ID: 5894832
• Journal Information: Basic Life Sci.; (United States), Journal Name: Basic Life Sci.; (United States) Vol. 23; ISSN BLFSB
• Country of Publication: United States
• Language: English

Related Subjects

560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
AROMATICS
BENZANTHRACENE
BIOLOGICAL PATHWAYS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BROMINATED AROMATIC HYDROCARBONS
CHO CELLS
CONDENSED AROMATICS
DNA
DOSE-RESPONSE RELATIONSHIPS
HALOGENATED AROMATIC HYDROCARBONS
HYDROCARBONS
MUTAGEN SCREENING
MUTAGENESIS
MUTANTS
NUCLEIC ACIDS
ORGANIC BROMINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
RECOVERY
REPAIR
SCREENING
TOXICITY