Th induction of thioguanine-resistant mutants of Chinese hamster cells by gamma-rays. 1977

J Thacker, and A Stretch, and M A Stephens

The induction of mutation to purine analogue resistance was assessed in Chinese hamster V79-4 cells exposed to gamma-radiation. After irradiation, the cells were grown in non-selective medium for different time intervals before respreading into medium containing 0.5-0.7 mug/ml thioguanine. In some experiments colonies arising in thioguanine-medium were counter-selected in medium containing the glutamine analogue azaserine, which distinguishes mutants with very little activity of the enzyme hypoxanthine-guanine phosphoribosyl transferase. Only these mutants were increased in frequency by radiation, the maximum measured frequencies occuring in cells respread after 2 days growth in non-selective medium. With longer intervals of post-irradiation growth in non-selective medium a fraction of the induced mutants was lost, and after large doses of radiation it is doubtful if the maximum frequency observed after 2 days post-irradiation growth represents the true induced frequency. The detection of freshly-induced mutants seemed to depend upon the dilution and decay of products formed from the genes prior to their mutation by radiation, since (a) selection of mutants in a higher concentration of thioguanine (2 mug/ml) increased the post-irradiation growth interval required to detect the maximum frequency of induced mutants, and (b) with increasing duration of post-irradiation growth in the non-selective medium, induced mutant cells were able progressively to overcome the growth-limiting effects of the analogue, to give large colonies when respread in thioguanine-medium. The radiosensitivities of 7 isolated mutant lines were indistinguishable from that of wild type cells, but the mutants were at a slight disadvantage when grown in competition with wild type cells. This disadvantage was consistent with the expected fitness of mutants relative to wild type cells calculated from estimates of the spontaneous mutation rate and the mean spontaneous mutation frequency. The induction of mutation to thioguanine resistance was non-linear with dose, yielding induced frequencies per rad of 5-10(-8) to 3-10(-7), but a plot of induced mutation frequency against log surviving fraction gave an approximately linear relationship. The same linear relationship holds for recently-published data on human and mouse cell cultures, so that all three mammalian cell types exhibit the same fixed probability of mutation induction relative to the extent of inactivation caused by ionising radiation.

UI MeSH Term Description Entries
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D011830 Radiation Effects The effects of ionizing and nonionizing radiation upon living organisms, organs and tissues, and their constituents, and upon physiologic processes. It includes the effect of irradiation on food, drugs, and chemicals. Effects, Radiation,Effect, Radiation,Radiation Effect
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004307 Dose-Response Relationship, Radiation The relationship between the dose of administered radiation and the response of the organism or tissue to the radiation. Dose Response Relationship, Radiation,Dose-Response Relationships, Radiation,Radiation Dose-Response Relationship,Radiation Dose-Response Relationships,Relationship, Radiation Dose-Response,Relationships, Radiation Dose-Response
D004351 Drug Resistance Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. Resistance, Drug
D013866 Thioguanine An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia. 6-Thioguanine,2-Amino-6-Purinethiol,Lanvis,Tabloid,Thioguanin-GSK,Thioguanine Anhydrous,Thioguanine Hemihydrate,Thioguanine Monosodium Salt,Thioguanine Tabloid,Tioguanina Wellcome,Tioguanine,2 Amino 6 Purinethiol,6 Thioguanine,Anhydrous, Thioguanine,Thioguanin GSK,ThioguaninGSK
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor

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