Mutation Research Letters最新文献

Thymine auxotrophy was shown to be associated with an increase in UV sensitivity both in Bacillus subtilis and in Escherichia coli. This UV sensitization became early evident in polA5 mutants of Bacillus subtilis: at UV doses of 16 J/m², a reduction of mor than 10-fold in the survivor population is observed in thymine requiring spontaneous mutants (polA5 thyA thyB) compared to the parental strains (polA5). Reversion of either thyA or thyB mutation led to a partial recovery in the UV resistance. This result suggests that DNA repair polymerization might be improved by the biosynthesis of thymidylate or some effect associated with such activity.

Experiments were carried out to ascertain whether or not coffee can modulate the genotoxicity of transplacentally active genotoxins/carcinogens. Coffee was orally administered to Swiss albino mice (gestation, 15–16 days), 90 min before exposure to cyclophosphamide (CPH), N-nitrosodiethylamine (DEN), N-nitroso-N-ethylurea (ENU) and mitomycin C (MMC). At the end of the treatment, the induction of micronucleated polychromatic erythrocytes (MnPCEs) was evaluated in the fetal liver (FL), feta blood (FB) and maternal bone marrow (MBM). The results of this transplacental micronucleus test showed a consistent trend which suggests that the administration of coffee instead of water (control) can significantly inhibit the genotoxic effects of CPH, DEN, ENU and MMC in the FL and FB. When the fetal cells were evaluated either 22 and 28 h after CPH treatment, or 24 and 48 h after MMC treatment, there was no evidence for a significant interaction between the sampling time and the inhibitory effect of coffee (two-factor) ANOVA). However, a significant interaction was observed between sampling time and the inhibitory effects of coffee when the fetal cells were sampled 24 and 40 h after DEN treatment (two-factor ANOVA). Coffee was also effective is significantly inhibiting the genotoxicity of CPH, ENU and MMC in the MBM. The differential response of fetal and maternal target cells was evident from this study.

Dopamine hydrochloride is reported to be a new mutagen precursor in this study. After treatment with nitrite under acidic conditions, dopamine hydrochloride showed direct-acting mutagenicity on Salmonella typhimurium TA100, TA98 and Escherichia coli WP2uvra. The addition of S9 mix did not affect the mutagenicity of nitrosated dopamine significantly in these three strains. Meanwhile, a comparison of the mutagenicity of nitrosated dopamine with nitrosated tyramine was carried out.

The mutagenicity of 12 simple benzoquinone (BQ) derivatives was studied using five different Ames Salmonella mutagenicity tester strains in the presence and absence of S9 mix. Seven of the BQs used displayed mutagenicity with and/or without S9 mix, and most of them produced a marginal increase in revertants. p-Benzoquinone (p-BQ) showed the most potent mutagenic activity (17 induced revertants/nmol/plate for strain TA104 without S9 mix) among the BQs tested. TA104, which is sensitive to oxidative mutagens, was the most sensitive to the mutagenicity of the BQs of the five strains used, while the second most sensitive strain was TA2637, which detects bulky DNA adducts. Significant reductions in the mutagenicity of p-BQ, and 2,3-diCl-5,6-diCN-BQ without S9 mix were observed in the presence of catalase. These findings suggest that the mutagenicity of BQs for S. typhimurium is attributable to oxidative injury after BQ reduction and to DNA adducts that form with BQs that have electrophilic substituents.

Starvation-association mutation to Tyr⁺ in E. coli WU3610 is identical to that in an isogenic derivative lacking reverse transcriptase encoded by a retron phage.

A new gene, designated dinP, was found during E. coli genomic sequencing around the 5.5 min region. Its coding region is preceded by a sequence similar to the consensus binding sequence for LexA, the so-called SOS box sequence. The amino acid sequence of DinP (351 amino acid residues) has a strong similarity to the C. elegans hypothetical protein F22B7.6 and weaker similarities to the UmuC homologues in E. coli and Salmonella typhimurium and also to REV1 of Saccharomyces cerevisiae. Another SOS operon (dinJ1 and dinJ2 genes) found in this region is also described.

Peripheral blood lymphocyte cultures of 116 smokers and 80 non-smokers who were occupationally exposed to uranyl compounds were analysed for sister-chromatid exchanges (SCEs). Blood samples were collected from 59 non-smokers (control group I) and 47 smokers (control group II) who were not exposed to uranium for control data. A significant increase in SCEs was observed among both smokers and non-smokers exposed to uranyl compounds when compared to their respective controls. In controls, a significant increase in the frequency of SCEs was observed in smokers when compared to non-smokers.

We have shown previously that certain alkylation products, or alkylation derived lesions, which induce chromosome aberrations (abs) persist for at least two cell cycles in Chinese hamster ovary cells. The increase in abs in the second cycle after treatment contrasts with the classical observation of reduction in ab yield with successive mitoses following ionizing radiation. Here we present evidence that processing of lesions by mismatch repair is a mechanism for ab induction by methylating agents.

Our previous studies implicated O⁶-methylguanine (O⁶MeG) as an important lesion in induction of abs, particularly in the second cell cycle after treatment. In the absence of repair of O⁶MeG by alkylguanine DNA alkyltransferase (AGT), new abs were induced in the second cycle after treatment with e.g. methylnitronitrosoguanidine (MNNG) and methylnitrosourea (MNU). Thus, we hypothesized that abs were produced not by O⁶MeG or its repair in the first S phase, but by subsequent processing of the lesions. We suggested that after replication proceeded past the O⁶MeG lesion in the first S phase, inserting an incorrect base on the newly synthesized strand, recognition and repair by mismatch repair in the second S phase led to a chromosome ab. Here we used MT1 cells, a human lymphoblastoid cell line that has a defect in strand-specific mismatch repair. MT1 cells are alkylation tolerant and have a mutator phenotype, compared with their parent line, TK6; both MT1 and TK6 cells lack AGT so do not remove the methyl group from O⁶MeG. While the initial levels of abs at the first metaphase were similar in MT1 and TK6 cells, ab levels in MT1 cells were greatly reduced in the second and third cell cycles following treatment with MNNG, dimethylnitrosamine and MNU, in contrast with the parent TK6 cells, which had more abs in the second cell cycle than in the first. This supports the hypothesis that repair of mismatched base pairs involving O⁶MeG is one mechanism for induction of chromosome abs. In contrast to the difference in response to methylating agents between TK6 cells and mismatch repair-deficient MT1 cells, the profile of ab induction by an ethylating agent, ethylnitronitrosourea, was similar in MT1 cells to those for TK6 cells and CHO cells.