Mouse L5178Y strain LY-S and its parental strain LY-R differ in their comparative sensitivities to the cytotoxic effects of various mutagenic agents-i.e., strain LY-S has been found to be more sensitive, less sensitive, or similarly sensitive to individual agents in comparison to strain LY-R. Nevertheless, strain LY-S has been found to be uniformly less mutable than strain LY-R at the hypoxanthine (guanine) phosphoribosyltransferase (Hprt) locus following treatment with x-radiation, UV radiation, or alkylating agents. In the present work we have isolated subclones of strains LY-R and LY-S that are heterozygous at the thymidine kinase (Tk) locus (chromosome 11). We have found that a heterozygous LY-S Tk+/Tk-strain shows as high or higher mutability at the Tk locus than do heterozygous LY-R strains following treatment with x-radiation, UV radiation, or ethyl methanesulfonate.Mutability of all heterozygous strains at the Tk locus is much higher than at the Hprt locus following treatment with these mutagenic agents, with the exception ofone heterozygous LY-R strain that possesses only one chromosome 11 and that is poorly mutable at the Tk locus by x-radiation. On the basis of these results, we have suggested that (i) because of a repair deficiency, multilocus lesions are formed in the DNA of LY-S strains following treatment with radiation or alkylating agents; (ii) multilocus lesions lead to poor recovery of viable mutants when the target locus is closely linked to essential genes and situated on a hemizygous chromosomal region (e.g., the Hprt locus on the X chromosome or the Tk locus in strains monosomic for chromosome 11); and (iii) x-radiation is a relatively poor mutagen at loci situated on hemizygous chromosomal regions, in repair-efficient and repair-deficient cells, because of its tendency to form multilocus lesions.Mouse lymphoma strain L-5178Y-S (LY-S) was first isolated by Alexander and Mikulski (1) following a spontaneous increase in the x-radiation sensitivity ofL5178Y cells growing in vitro. The parental strain was named L5178Y-R (LY-R) to differentiate it from the newly isolated sensitive strain. In spite of the greater sensitivity of strain LY-S to the cytotoxic effects of x-radiation and alkylating agents (2-5), strain LY-S is less mutable than strain LY-R by UV radiation and x-radiation and by alkylating agents at the hypoxanthine (guanine) phosphoribosyltransferase (Hprt) and Na+,K+-ATPase loci (4-6). In the present work we have compared the mutability of the two strains at the thymidine kinase (Tk) locus situated on chromosome 11 (7, 8) using heterozygous Tk+/Tk-strains of LY-R and LY-S. We have found the mutability of the heterozygous LY-S strain (LY-Si) to be as high or higher than that of LY-R heterozygous strains (LY-R16 and LY-R83) at the Tk locus following treatment with x-radiation, UV radiation, or ethyl methanesulfonate (EtMes). Mutant frequencies are much higher at the Tk locus than at the Hprt and Na',K+-ATPase loci for LY-S and LY-R heterozygous strains treated with these age...

The cytotoxic and mutagenic effects of chloroaluminum phthalocyanine (CAPC) plus red light have been measured in strains of L5178Y mouse lymphoma cells which differ in their DNA repair capacities. Strain LY‐R, deficient in the excision repair of UV‐induced dimers, was found to be relatively more sensitive to the cytotoxic effects of CAPC plus light, whereas strain LY‐S, deficienl in the repair of DNA double‐strand breaks, was more sensitive than strain LY‐R to the mutagenic effects of the treatment. Mutation frequencies were measured in LY‐S and LY‐R sub‐strains which were heterozygous or hemizygous at the thymidine kinase (tk) locus. The mutation frequency at the tk locus induced in the heterozygous strain LY‐SI by CAPC plus light was lower than that induced by an equitoxic dose of ionizing radiation but similar to that induced by an equitoxic dose of UVC radiation: The mutation frequency at the F., dose of CAPC plus light was approximately 1100 per 106 surviving cells. The induced frequency in strain LY‐S1 was much higher than in either tk+l‐heterozygous or ik+10 hemizygous strains of LY‐R. The rate and extent of incorporation of CAPC by the LY‐R strains was somewhat greater than for strain LY‐S1 at early times after CAPC addition, but by the time the cells were irradiated (18 h after CAPC addition) the difference was not great enough to account for the difference in cytotoxicity. It is possible that the cytotoxic and mutagenic lesions differ and that either the quantities of the respective lesions induced or the efficiencies of repair of the respective lesions differ inversely in the two strains. light have been measured in strains of L5178Y mouse lymphoma cells which differ in their DNA repair capacities. Strain LY‐R, deficient in the excision repair of UV‐induced dimers, was found to be relatively more sensitive to the cytotoxic effects of CAPC plus light, whereas strain LY‐S, deficienl in the repair of DNA double‐strand breaks, was more sensitive than strain LY‐R to the mutagenic effects of the treatment. Mutation frequencies were measured in LY‐S and LY‐R sub‐strains which were heterozygous or hemizygous at the thymidine kinase (tk) locus. The mutation frequency at the tk locus induced in the heterozygous strain LY‐SI by CAPC plus light was lower than that induced by an equitoxic dose of ionizing radiation but similar to that induced by an equitoxic dose of UVC radiation: The mutation frequency at the F., dose of CAPC plus light was approximately 1100 per 106 surviving cells. The induced frequency in strain LY‐S1 was much higher than in either tk+l‐heterozygous or ik+10 hemizygous strains of LY‐R. The rate and extent of incorporation of CAPC by the LY‐R strains was somewhat greater than for strain LY‐S1 at early times after CAPC addition, but by the time the cells were irradiated (18 h after CAPC addition) the difference was not great enough to account for the difference in cytotoxicity. It is possible that the cytotoxic and mutagenic lesions differ and that either the quantities of the respective...

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We have developed a model to calculate the dose to the cell nucleus in cells exposed in suspension to radon and/or radon progeny. The model addresses the influence of (1) different radiation qualities and energies in the irradiation milieu; (2) the contribution to dose from radioactivity in the medium surrounding the cell after exposure to the radon gas as well as that from excess radon progeny associated with the cell; (3) the geometry of the cell and of the radiosensitive target, the cell nucleus; (4) the intracellular localization of the radionuclides; (5) attenuation of the alpha particles by the cytoplasm; (6) the radionuclide concentrations in the medium; and (7) the length of exposure. Investigation of the influence of these various parameters was made using an irradiation system in which cells were exposed to 212Bi, which decays to stability with the emission of an alpha particle (either 6.05 or 8.78 MeV). The information from these studies was then used to develop the system further for more complex systems in which 222Rn and its progeny are present. The model takes into account the contribution of dose from different radiation sources using scintillation counts of the medium and the cells, and it is useful for calculations of dose in situations where cells are exposed in suspension culture.