Relative sensitivity of V79 and V79/79 cells to spontaneous and induced mutation to 6-thioguanine and ouabain resistance

Abstract

The relative responses of V79 and V79/79 cells to mutation to 6-thioguanine (6TG R) and ouabain resistance (OUA R) have been compared in unmutagenized cells and after exposure to ethyl methanesulphonate (EMS), N-methyl- N-nitrosourea (MNU) and ultraviolet light. In the V79/79 cell line, the spontaneous frequency of 6TG R colonies but not of OUA R colonies was enhanced compared to that in V79 cells. This appears to be the result of a reduced growth rate and plating efficiency of V79/79 cells and does not reflect a real difference in spontaneous mutability. V79/79 cells were more sensitive than V79 to the cytotoxic effects of all three mutagens, but induced mutation by UV, EMS and MNU to 6TG R was similar in the two cell lines. The lack of a differential response for induced mutation to 6TG R may reflect: (a) differences in selective stringency of thioguanine in the two cell lines, and (b) the greater susceptibility of V79/79 cells to induced chromosome damage. The relative mutability of the cell lines to OUA R was dependent on the mutagen used. V79 cells were significantly more mutable than V79/79 cells after MNU exposure, but the two cell lines were similar in sensitivity to EMS-induced mutation. After UV-irradiation, however, V79/79 cells were more mutable than V79 cells. The differential response of the two cell lines to MNU suggests that O 6-methylguanine is potentially mutagenic in V79 cells but is both potentially lethal and potentially mutagenic in the more sensitive V79/79 cells. The absence of a differential response to EMS-induced mutagenesis suggests that methylated and ethylated bases are repaired differently in Chinese hamster cells. The hypermutability of V79/79 cells by UV-irradiation indicates that thymine dimers are potentially lethal and potentially mutagenic in both cell lines.