No abstract available

[en] Through a new approach, we have sought to isolate ultraviolet light (UV)-sensitive and DNA repair mutant Chinese hamster fibroblasts. The procedure consisted of 1) mutation induction by 5-bromodeoxyuridine (Brd U)-blacklight and UV treatments; 2) incorporation of 3H-thymidine in repair-proficient cells at high temperature (38.5 degrees C) following UV damage; 3) cold holding (4.0 degrees C) of these cells to induce tritium killing; and 4) recovery and testing of repair-deficient and UV-sensitive cells which have survived and formed colonies at low temperature (34.0 degrees C). In our initial attempt at this protocol, we isolated 72 surviving colonies from 2 x 10(7) cells plated for selection. Of the 72 colonies, 20 demonstrated potential interest and four were selected for extensive study. One, identified as UVs-7, is slightly more sensitive to UV, but not sensitive to X rays or N-acetoxy-2-acetylaminofluorene (NAc-AAF). The mutant exhibits a highly reduced level of unscheduled DNA synthesis (UDS), as compared to the parental line. Two additional lines, UVs-40 UVs-44, are sensitive to UV, X ray, N-methyl-N-nitro-N-nitrosoguanidine (MNNG), and NAc-AAF, but exhibit normal UDS. A fourth line, UVr-23, has enhanced UDS, is resistant to UV, but exhibits no difference in sensitivity to x ray or NAc-AAf. These mutants are all stable, and should be useful for the study of mammalians DNA repair processes and mechanisms of mutagenesis

No abstract available

No abstract available

[en] We have previously reported the isolation and partial characterization of DNA repair and/or mutagen-sensitive mutant Chinese hamster cell strains. Here we present the results of a detailed study of the ultraviolet light (UV)-induced mutability of one of these strains, UVs-7, and provide preliminary mutability data on two additional lines, UVr-23 and UVs-40. UVs-7 in extremely deficient in unscheduled DNA synthesis (UDS) but only slightly more sensitive to UV than the parental line. When examined for the UV-inducibility of mutants resistant to ouabain, 6-thioguanine, or diphtheria toxin, UVs-7 was found to be hypermutable at all three loci as compared to the parental line. The degree of hypermutability was not the same for any two loci. UVs-40, a highly UV-sensitive strain, was also found to be hypermutable at the ouabain-resistant (ouar) locus. UVr-23, which is UV-resistant and more proficient at UDS than the parental line, appeared to exhibit a tendency toward hypomutability at both the ouabain(ouar) and 6-thioguanine--resistant (6TGr) loci. Further characterization of all these lines should aid in delineating mammalian mechanisms of DNA repair and mutagenesis

[en] Health in a multicellular organism is maintained by homeostatic processes. Disruption of these homeostatic controls at the molecular, biochemical, cellular, and organ systems levels can be brought about by irreversible changes in the genetic material (mutagenesis), cell death (cytotoxicity), or reversible changes in the expression of genes at the transcriptional, translational, or posttranslational levels (epigenesis). While radiation is known to induce DNA damage/mutations, cell, death and epigenetic changes, in addition to cancers that are found in radiation-exposed animals, experimentally, and in humans, epidemiologically, the question is, At low-level exposure, what is the risk that cancers are open-quotes causedclose quotes by the radiation?

[en] Pyrimidine dimer production and excision in epidermal DNA were studied at five different dose levels of ultraviolet light in the skin of intact mice. Dimer production increased with dose up to 50,400 ergs/sq mm. Approximately 30 percent of the thymine-containing dimers were excised by 24 hr after irradiation at three lower dose levels of ultraviolet light. Nonsemiconservative DNA replication in ultraviolet-irradiated mouse skin was shown to continue for at least 18 hr. The rate of nonsemiconservative replication decreased with time, but did so slowly. The initial rates of nonsemiconservative replication increased with ultraviolet light dose levels up to about 4200 ergs/sq mm, after which the initial rates were decreased. Semiconservative epidermal DNA synthesis was shown to be inhibited by hydroxyurea, but hydroxyurea had no effect on ultraviolet light-induced nonsemiconservative DNA replication. The observed pyrimidine dimer excision and nonsemiconservative DNA replication suggest that in the intact mouse the cells of the epidermis are capable of DNA excision repair after ultraviolet irradiation of mouse skin

[en] The aim of this paper is to understand how low dose radiation contributes to the formation of cancers. A brief review of both the major theories of carcinogenesis and mechanisms of action of radiation is undertaken. Nature of carcinigenesis is first discussed, focusing on the fact that it is a complex multi-step process, each step of which might have multi-mechanisms and each step being mechanistically different fromt the others. Implications to radiation induced carcinogenesis is then discussed. Theoretical evidence provides that ionizing radiation, as an efficient clastogen and inducer of deletion mutations, might be affecting any of the three steps (e.g., deleting regulator genes controlling oncogenes; rearranging oncogenes to have altered expression; causing cell death to promote surviving stem cells initiated by other agents; and deleting tumor suppressor genes). The stem cell pool, at the time of acute ionizing radiation, the number of initiated cells in the body and the amount of cell killing induced by a given dose of ionizing radiation would all contribute to the carcinogenic process. (N.K.)

[en] The role on unrepaired DNA lesions in the production of mutations is suspected of contributing to the initiation phase of carcinogenesis. Since the molecular basis of mutagenesis is not understood in eukaryotic cells, development of new genetic markers for quantitative in vitro measurement of mutations for mammalian cells is needed. Furthermore, mammalian cells, genetically deficient for various DNA repair enzymes, will be needed to study the role of unrepaired DNA lesions in mutagenesis. The results in this report relate to preliminary attempts to characterize the diphtheria toxin resistance marker as a useful quantitative genetic marker in human cells and to isolate and characterize various DNA repair-deficient Chinese hamster cells

[en] Nontoxic concentrations of harman and norharman were tested in cultured Chinese hamster cells for their effects on DNA repair and mutagenesis. The following effects of harman were observed: (a) the survival of ultraviolet light- or x-ray-damaged cells was reduced; (b) the ultraviolet light-induced unscheduled DNA synthesis was slightly inhibited; and (c) the frequency of spontaneous or ultraviolet light-induced ouabain-resistant (ouar) or 6-thioguanine-resistant (6-TGr) mutations was reduced. Furthermore, the effect of harman on survival and mutagenesis was greater than that of norharman and was detected primarily in treatments in which cells were exposed to harman immediately following ultraviolet light irradiation. Our data clearly indicate that harman decreases the capacity to repair DNA damage and fix mutations in Chinese hamster cells, possibly because of the intercalation properties of this compound