Mutation Research Letters最新文献

The single cell gel test (SCG test or comet assay) was used to study DNA damage in peripheral white blood cells (WBC) of humans after a single bout of exhaustive exercise and the effect of vitamin supplementation. Human subjects were asked to run on a treadmill until exhaustion and blood samples were taken before and 24 h after the run. A clear increase in DNA strand breakage was observed in the 24-h sample of all probands. A short-term application of multivitamin pills or vitamin E (3 × 800 mg) resulted in a significantly smaller increase of DNA effects in WBC of some probands. When the volunteers were given a supplement of vitamin E (1200 mg daily) for 14 days prior to run, exercise-induced DNA damage was clearly reduced in all probands. In four out of five subjects, vitamin supplementation completely prevented the induction of DNA damage after exhaustive exercise. Intake of vitamin E for 14 days led to a clear increase in vitamin E serum concentrations. Malondialdehyde (MDA), a marker of lipid peroxidation, was measured in the serum of probands in tests with and without vitamin supplementation for 14 days. MDA concentrations were significantly decreased following vitamin E supplementation but not significantly changed 15 min and 24 h after a run. Our results demonstrate that vitamin E prevents exercise-induced DNA damage and indicate that DNa breakage occurs in WBC after exhaustive exercise as a consequence of oxidative stress.

This study emphasizes the problems encountered in obtaining suitable contol levels for comparison with occupational studies of exposure to clastogens.

Blood samples taken from 135 individuals (69 females and 66 males) were examined for chromosome aberrations. The data include 15 368 cells scored for chromosome aberrations. The frequencies of chromatid and chromosome breaks, acentric fragments and dicentrics were determined. The frequency of the most common chromosome aberration, chromosome breaks, was 1.1 x 10^-2 and for dicentries 0.26 x 10³. The values obtained were investigatd in relation to sex, cigarette smoking habits, diagnostic X-ray exposure and use of antibiotics. In all the parameters, no significant differences were found.

Some chemical carcinogens localize preferentially in mitochondrial DNA (mtDNA) when compared with genomic DNA (gDNA). Here we compare the ability of cisplatin (cis-diamminedichloroplatimum[II]) to induce DNA adducts in both genomic and mtDNA of Chinese hamster ovary (CHO) cells in culture. Cytotoxicity was examined by cell survival 4, 8 and 24 h afer exposure to 50 μM cisplatin. Cisplatin-DNA adducts were measured in DNA from nuclear and mitochondrial fractions by dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA), a sensitive competitive microtiter-based immunoassay utilizing antiserum elicited against cisplatin-modified DNA. An additional comparison of cisplatin-DNA binding in both compartments was performed by immunoelectron microscopy using the cisplatin-DNA antiserum and colloidal gold. DELFIA analysis of cisplatin-DNA adducts in gDNA and mtDNA showed a six-fold higher incorporation of drug into mtDNA as compared to gDNA. Morphometric studies of colloidal gold distribution in photomicrographs of CHO cells showed mtDNA to contain a four-fold higher concentration of cisplatin as compared to nuclear DNA. Therefore, both methods demonstrated a preferential binding of cisplatin to mtDNA versus gDNA.

The effect of 1,3-dimethyl-2-thiourea (DMTU), a specific hydroxyl radical scavenger on chromate-induced DNA breaks, was studied using Chinese hamster V-79 cells. Incubation of cells with Na₂CrO₄ plus DMTU resulted in a small but significant decrease in cellular levels of the metal-caused DNA single-strand breaks. Electron spin resonance studies showed that DMTU did not affect the formation of chromium (V) complexes either in cells or in the reaction of Na₂CrO₄ with reduced glutathione in vitro, however, DMTU suppressed the generation of hydroxyl radicals in the reaction of hydrogen peroxide and chromium (V) in vitro. Thus, Na₂CrO₄-induced DNA breaks were inhibited by DMTU, possibly due to its ability to scavenge hydroxyl radicals. These and other previous studies indicated that the formation of hydroxyl radicals contribute to the induction of DNA breaks by Na₂CrO₄ in intact cells, but presumably is not the only mechanism involved.

We have molecularly characterized the SNG1 gene that confers hyper-resistance to the mutagen N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) in Saccharomyces cerevisiae when overexpressed on a multi-copy plasmid. This hyper-resistance to MNNG is not due to depletion of glutathione pools since multi-copy SNG1 containing yeast transformants contain at least wild type levels of glutathione; DNA repair seems unaffected in these transformants as the multi-copy SNG1-mediated MNNG hyper-resistance is also seen in DNA repair mutants belonging to each of the three epistasis groups of yeast repair mutants. It could be shown that SNG1 is not under control of the YAP1 encoded transcription activator that controls expression of at least two genes involved in MNNG metabolism in yeast, sng1 null mutants are viable but exhibit only slight sensitivity to MNNG, indicating that SNG1 does not encode a protein involved in a major detoxification step of this mutagen. Sequencing of the HYR-mediating passenger DNA revealed that SNG1 encodes a 547 aa polypeptide containing seven transmembrane-spanning regions that may be membrane-bound. Comparison of the DNA sequence with established gene databanks revealed that SNG1 is a novel yeast gene.

The genotoxicity of deltamethrin was studied in Swiss albino male mice (five animals/group) using the bone marrow micronucleus assay. Deltamethrin (two i.p. injections, 30 h and 6 h before sample collection) was found to induce micronuclei at 162.5 and 300.0 mg/kg body weight. A lower dose (32.5 mg/kg body weight) failed to induce a significant increase in micronuclei over the control level.

Escherichia coli and Salmonella typhimurium strains decifient in the OxyR-regulated adaptive response to oxidative stress were used to study the mode in which spontaneous SOS-dependent mutations are generated in a distressed bacterial population. When assayed on supplemented selective medium, the E. coli strain IC3821 (trpE65), carrying the ΔoxyR30 mutation and containing the plasmid pRW144 (mucA/B), showed a frequency of spontaneous Trp⁺ revertants similar to that of the oxyR⁺ control. Instead, the IC3821 strain exhibited an enhancement in the clonal occurrence of spontaneous revertants arising at random during growth on a nonselective medium. A similar enhancement was observed for the S. typhimurium strain TA4125 (hisG428 ΔoxyR2). The mutator effect observed in oxyR⁻ cells would be induced by an increased background of reactive oxygen species; it provides a model for studying the mutability of a cell population constantly exposed to mutation-inducing agents. In the IC3821 strain, revertants were induced by f-butyl hydroperoxide with higher efficiency than in oxyR⁺. We suggest that strain IC3821 could be useful for the detection of SOS-dependent mutagenesis induced by chemical oxidants.

This is the first report of clastogenic effects of chlorinated hydroxyfuranones (CHFs) in plants. Two byproducts of water chlorination, 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX) and 3,4-dichloro 5-hydroxy-2[5H]-furanone (MA) induced a dose dependent increase of micronuclei (MN) in pollen mother cells of Tradescantia when doses up to 100 μg MX and 500 μg MA were applied directly to the inflorescences. In contrast, exposure of the stems in aqueous solutions containing up to 1 mg/I MX and 10 mg/I MA did not cause a positive response.

Incubation of human peripheral blood cultures in the presence of an electromagnetic field (EMF) of 50 Hz and 5 mT leads to stimulation of the cell cycle of dividing lymphocytes but has no influence on the frequencies of sister-chromatid exchanges. Comparative studies with two different exposure systems and with different culture temperatures indicate that the effect on the cell cycle results from the EMF and is not a thermal effect. These data support the assumption that with respect to their suspected carcinogenic effects EMFs have no initiating but probably promoting effects.