Mutation Research Letters最新文献

Ortho-meta-and para-nitrobenzyl bromides alcohols ethers and esters were synthesized and tested for their mutagenicity toward Salmonella typhimurium TA100, TA100NR (nitroreductase deficient) and TA98 in absence of S9 mix and in TA100 with S9 mix. Compounds of the ortho-and meta-series were non mutagenic with and without S9 mix. Except for the alcohol and ether, the compounds of the para-series were mutagenic in TA100 with activity sequence propionate > butyrate > benzoate > acetate > bromide and this specific activity was reduced considerably by S9 mix. The Ames Salmonella test system does not seem to be an appropriate model to evaluate mutagenicity of o-nitrobenzyls. However, further work is in progress to test all the compounds for mutagenicity in mammalian system

The inducible ability of adaptive response by low doses of gamma rays or bleomycin was studied in peripheral blood lymphocytes of healthy donors and in ataxia telangiectasia patients. An adaptive response was found in the lymphocytes of healthy donors pretreated with either gamma rays or bleomycin, however in individuals heterozygous for ataxia only bleomycin was effective. In the two ataxia telangiectasia homozygotes tested no adaptive response was found either after low-dose gamma rays or after bleomycin. The preliminary results indicate that the adaptive response might be infuenced by various factors.

XRCC1 is a DNA repair gene involved in rejoining DNA strand-breaks. We used baboon as an animal model to determine the levels of XRCC1 gene expression in different tisues. Baboons were selected because they are evolutionarily closely related to humans. A single 2.2 kb transcript was detected in all tissues tested by northern blot analysis, with variations in levels of expression among tissues. The expression levels of XRCC1 were measured by quantitative RNase protection assays. XRCC1 mRNA levels were significantly higher in testis than those other tissues. A mean value of 24.6 × 10⁵ XRCC1 transcripts per μg DNA was found in testis, while 10.5 × 10⁵ in ovary, 9.8 × 10⁵ in brain, 8.5 × 10⁵ in liver, 6.8 × 10⁵ in kidney, 6.5 × 10⁵ in heart, 6.4 × 10⁵ in lymph nodes, 6.0 × 10⁵ in lung and 4.9 × 10⁵ in spleen were found.

The effect of interferon-α or β on platinum analogues [cisplatin (CDDP) and carboplatin] cytotoxicity was studied in four glioblastoma cell lines (U373MG, T98G, A172 and U118Mg). All cell lines were strongly resistant to the cytotoxic effect of CDDP or carboplatin. Although both interferons were not cytotoxic in all cell lines, they were able to significantly increase the cell platinum-sensitivity. Specifically interferon-α increased the magnitude of CDDP-induced DNA interstrand crosslinks

Our findings suggest that interferons are able to induce a very strong potentiation of platinum analogues cytotoxicity in drug-resistant human glioma cell lines

In an earlier work stable aberrations and dicentrics were determined by fluorescence in situ hybridization (FISH) after various doses of ¹³⁷Cs γ-rays. No corresponding calibration curve for dicentrics is available for determinations in terms of the conventional analysis as performed in our laboratory, In view of the potential for the application of chromosome painting to human biological dosimetry, it is desirable to determine such a calibration curve and this and the comparison of the resulting data to those obtained in terms of the FISH method is the objective of the present communication. In the study it is found that the linear-quadratic dose response curves for dicentrics, that are determined by the two methods, are significantly different, although the different target sizes are accounted for. A similar problem was found earlier for X-rays. It does not appear that the difference is due to technical difficulties in the FISH method, that has been improved by employing in addition to the whole chromosome DNA probes, a pan-centrometric DNA probe

Previous authors investigated individual responsiveness to mutagens by assessing cytogenetic damage following gin vitro treatment. Diepoxybutane (DEB) has been used to assess chromosome instability both in repair-deficient and normal subjects. Since bimodal distribution of sister chromatid exchanges (SCEs) or chromosomal aberration (CAs) frequencies has been observed in normal subjects, we investigated the possible factors determining the ‘high-respondent’ phenotype. The bimodal-shaped distribution suggested the presence of a single factor responsible far this phenotype. Our data showed that red blood cells are involved in determining the sensitivity of lymphocytes to DEB induced SCE. The existence of a polymorphic factor in red cells involved in DEB detoxification is suggested.

3-chloro-4(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) was tested without exogenous activation in L51785/TK^+/−-3.7.2C mouse lymphoma cells for mutation at the thymidine kinase locus and for clastogenicity. At a concentration of 0.75 μg/ml, the induced mutant frequency was 1027 per 10⁶ survivors (survival = 11%). A concentration-related increase of large and small colony mutants was observed, but the majority of the MX induced mutants formed small colonies, consistent with the positive clastogenic response that was observed. MX primarily induced chromatid breaks and rearrangements (30 chromatid and 4 chromosome aberrations per 100 cells) at the 0.75 μg/ml dose. These studies indicate that MX induces a broad spectrum of genetic damage.

The T-cell-cloning assay wa established to determine the frequency of hypoxanthine-guanine phosphoribosyl-transferase (HPRT) mutant lymphocytes in the presence of the selective agent 6-thioguanine in peripheral blood from a human control population. We investigated 44 healthy adults (blood donors) and found a mean mutant frequency of 7.2 × 10⁻⁶ (geometric mean 5.6 × 10⁻⁶). An elevted mean mutant frequency occurred in smokers as compared to non-smokers. However, a statistically significant increase was only observed between female smokers and female non-smokes while there was only a slight difference in the male group. A significant difference in mutant frequency could be found between individuals younger than 35 years and those above 35. But the difference of the mutant frequency with age showed up only among smokers. No significant effect of the gender was observed. Mutant frequency was inversely related to the cloning efficiency.

The antigenotoxic effects of curcumin, including the inhibition of SOS induction and mutagenesis by UV light, were investigated in Salmonella typhimurium TA1535/pSK1002 and Escherichia coli K-12 strains. Induction of the SOS gene (umuC) expression was assayed by measuring accumulated β-galactosidase activity. We found that curcumin blocked umuC induction promoted by UV irradiation in a dose-dependent manner. Also, with another SOS response, Weigle reactivation, we observed that curcumin effectively inhibited phage reactivation by UV irradiation. Furthermore, we tested the effect of curcumin on UV mutagenesis. We showed that mutagenesis induced by UV irradiation was suppressed by the addition of curcumin. Together these results indicate that curcumin acts as an inhibitor of SOS functions including UV mutagenesis.

Distributions of 1,3-dinitropyrene (1,3-DNP), 1,6-DNP, 1,8-DNP, 1-nitropyrene (1-NP) and mutagenicity in airborne particulates collected in downtown Kanazawa, Japan with an Andersen high-volume air sampler were examined. Mutagenicities of benzene-ethanol extract from particulates were determined by the Ames test using S. typhimurium strains with S9 mix, while concentrations of DNPs and 1-NP were determined by high-performance liquid chromatography (HPLC) using chemiluminescence detection. In the finest particulate fraction (smaller than 1.1 μm), 68% and 75% of the total mutagenicities were observed in TA98 and YG1024 strains, respectively. In the same fraction, 65–82% of three DNPs as well as 84% of 1-NP were observed. Mutagenic contributions of 1,3-DNP, 1,6-DNP, 1,8-DNP and 1-NP in the extract were respectively 0.6, 1.2, 1.8 and 1.6% in the TA98 stain, and 2.5, 5, 9 and 2.1% in the YG1024 strain.