煤尘提取物的遗传毒性研究

本研究系采集山西省８个大矿务局所属的１０个煤矿，井下掘进工作面煤样１６份，包括７种煤、即烟煤、无烟煤，弱粘结煤，肥煤，瘦煤、焦煤、气煤，每一份煤将经提取，分成丙份；一份进行亚硝化，另一份为非亚硝化煤样，分别进行Ａｍｅｓ试验，ＳＯＳ显色试验，双微核试验，大鼠骨骼细胞染色体为分骅结果表：１６份煤样提取物经亚硝化后，其中有１０种Ａｍｅｓ试验。ＳＯＳ显色试验均为阳性，从１０种阳性煤尘中，选１至３种进行染色     

Mutagenic activity in waste from an aluminum products factory in Salmonella/microsome assay

The mutagenic activity of waste material originating from an aluminum products factory was determined by the Salmonella/microsome assay, using the bacterial strains TA100, TA98 and YG1024. The material was obtained by sweeping the factory floor at the end of the work shift. Organic compounds were extracted by ultrasound for 30 min in dichloromethane or 70% ethanol. After evaporation of solvent, these extracts were dissolved in dimethylsulfoxide, and tested for the mutagenic activity at varying concentrations. All the extracts from the factory had mutagenic activity, especially in the YG1024 strain, suggesting the presence of aromatic amines, later confirmed by chemical analysis. The TA98 strain also showed mutagenic activity, though it did not exhibit the highest mutagenicity index observed with the YG1024 strain. In TA100, mutagenic activity was not observed. This study should serve as an alert to management and those who are occupationally exposed, and as a warning that this type of waste should not be discarded in the environment without any control.     

Antimutagenic potential of the Thai herb, Mucuna collettii Lace

Mucuna collettii Lace is a Thai herb with a long record of consumption among mature Thai males for the promotion of sexual potency. The mutagenic and antimutagenic potentials of Mucuna collettii extract were carried out by using the Ames test pre-incubation method in the presence and absence of S9 mixture. Salmonella typhimurium strains TA 98 and TA 100 were applied as the tester strains. Prior to mutagenic and antimutagenic tests, the survival of the tester strains was performed by treating with the plant extract. Results showed Mucuna collettii extract exhibited strong cytotoxic effects in a dose-dependent manner. Toxicity of the plant was confirmed in mice in which negative adverse effect was found in kidney, uterus, ovary, and testis. Mucuna collettii extract in the presence and absence of S9 mixture was negative for mutagenic Ames test. Mucuna collettii extract in the presence and absence of S9 mixture was positive for antimutagenic Ames test towards either one or both of the tested mutagens: 2-(2-furyl)-3-(5-nitro-2-furyl)-acrylamide (AF-2) and benzo(a)pyrene. The antimutagenic activity of the plant extract was confirmed in rec-assays. Micronucleus test demonstrated that Mucuna collettii extract at high dose and a long incubation time could induce micronucleus formation in tested animals, but less than the response of the positive control. The overall mutagenic and antimutagenic assays are further evidences for the antimutagenic potential of Mucuna collettii.     

稀土硝酸盐致突变效应研究

本文应用六种稀土硝酸盐在Ａｍｅｓ法对ＴＡ９８有ＴＡ１００菌测试中的回变菌落数与阴性对照的自发回变菌落数基本一致，显示无致突变作用；而硝酸铈在每皿５０μｇ－５０００μｇ时，能减少２ＡＦ的致突变菌落数，表现出抗旅为反应。     

Metabolic studies on the possible mode of action of isoniazid tumorigenicity

Summary Data on tumorigenicity and mutagenicity of INH show that INH is tumorigenic in mice but not in rats. The metabolic studies on the two species denote that rats are rapid inactivators whereas mice are slow inactivators of INH. Rats are also resistant to the immediate inhibitory effect of INH on DNA biosynthesis. Using Ames test it was observed that INH is mutagenic to salmonella typhimurium strains TA 100 and 1535 and this effect is abolished in presence of 59 mixture. In vivo and in vitro studies on INH interaction with macromolecules reveal that there is a greater interaction with RNA than with DNA and the site of interaction is the cytidine and deoxycytidine, respectively. A preliminary study is undertaken to see if healed TB cases have a higher risk for cancer. It is found that cancer incidence in this group is higher as compared to noncancer patients.     

Mutagenic activity promoted by amentoflavone and methanolic extract of Byrsonima crassa Niedenzu

Byrsonima crassa is a plant pertaining to the Brazilian central savannah-like belt of vegetation and popularly used for the treatment of gastric dysfunctions and diarrhoea. The methanol extract contains catechin, tannins, terpenes and flavonoids; both mutagenic potential and antioxidant properties have been ascribed to flavonoids. The mutagenicity of some flavonoids is believed to be associated with the formation of reactive oxygen species and seems to depend on the number and position of hydroxyl groups. In the present study the mutagenic activity of the methanol, chloroform and 80% aqueous methanol extracts, as well as acetate and aqueous sub-fractions, of this medicinal plant were evaluated by Salmonella typhimurium assay, using strains TA100, TA98, TA102 and TA97a, and in mouse reticulocytes. The results showed mutagenic activity of the methanolic extract in the TA98 strain without S9, but no mutagenicity to mouse cells in any of the extracts. The acetate fraction showed strong signs of mutagenicity without S9, suggesting that in this enriched fraction were concentrated the compounds that induced mutagenic activity. The aqueous fraction showed no mutagenic activity. The TLC and HSCCC analyses of the acetate fraction with some standard compounds permitted the isolation of the quercetin-3-O-beta-D-galactopyranoside, quercetin-3-O-alpha-L-arabinopyranoside, amentoflavone, methyl gallate and (+)-catechin, of which only the amentoflavone exhibited positive mutagenicity to TA98 (+S9, -S9).     

Cytogenetic effect of ortho-phenylenediamine in the mouse,Chinese hamster,and Guinea pig and of derivatives,evaluated by the micronucleus test

The mutagenic potential of ortho-phenylenediamine — known by studies on Salmonella typhimurium — was studied in mice, Chinese hamsters and Guinea pigs with the use of the micronucleus test. In bone marrow of all three species, chromosomal damage was detected following intraperitoneal injections of the test chemical, this damage was seen also after peroral administration to mice. Four derivatives of ortho-phenylenediamine containing one or two methyl-, nitro- or chlorosubstituents in 4- or 5-position of the aromatic ring were studied in mice. Of these the 4-methyl-derivative induced micronuclei, the 4-nitro-, 4,5-dimethyl-, and 4,5-dichloroderivatives were inactive. The results indicate that the chemical nature and the number of substituents influence the chromosome damaging potential.     

Direct repeats in mitochondrial DNA and mammalian lifespan

Mitochondria have long been suspected to be among the leading determinants of aging due to their functional importance and accelerated deterioration caused by accumulation of mutations in the mitochondrial DNA. Direct repeats are known to contribute to deletion formation in mtDNA and are a powerful source of reactive oxygen species (ROS)-independent mutagenesis. To evaluate the potential importance of homology-based deletion formation, we have analyzed the association between direct repeats in the mtDNA sequence and the lifespans of 65 mammalian species. Here, we report a significant negative correlation between the mutagenic potential of direct repeats and the mammalian lifespan, which is especially evident in closely related species.     

Potentially mutagenic impurities: Analysis of structural classes and carcinogenic potencies of chemical intermediates in pharmaceutical syntheses supports alternative methods to the default TTC for calculating safe levels of impurities

Potentially mutagenic impurities in new pharmaceuticals are controlled to levels with negligible risk, the TTC (threshold of toxicological concern, 1.5 μg/day for a lifetime). The TTC was based on the more potent rodent carcinogens, excluding the highly potent “cohort of concern” (COC; for mutagenic carcinogens these are N-nitroso, Aflatoxin-like, and azoxy structures). We compared molecules with DEREK “structural alerts” for mutagenicity used in drug syntheses with the mutagenic carcinogens in the Gold Carcinogenicity Potency Database. Data from 108 diverse synthetic routes from 13 companies confirm that many “alerting” or mutagenic chemicals are in structural classes with lower carcinogenic potency than those used to derive the TTC. Acceptable daily intakes can be established that are higher than the default TTC for many structural classes (e.g., mono-functional alkyl halides and certain aromatic amines). Examples of ADIs for lifetime and shorter-term exposure are given for chemicals of various potencies. The percentage of chemicals with DEREK alerts that proved mutagenic in the Ames test ranged from 36% to 83%, depending on structural class, demonstrating that such SAR analysis to “flag” potential mutagens is conservative. We also note that aromatic azoxy compounds need not be classed as COC, which was based on alkyl azoxy chemicals.     

Lack of mutagenic effect by multi-walled functionalized carbon nanotubes in the somatic cells of Drosophila melanogaster

Carbon nanotubes (CNTs) are formed by rolling up a single graphite sheet into a tube. Among the different types of CNTs, the multi-walled carbon nanotubes (MWCNTs) comprise a set of concentric nanotubes with perfect structures. Several uses for MWCNTs have been suggested to be included in biological applications such as manufacturing of biosensors, carriers of drugs. However, before these materials can be put on the market, it is necessary to know their genotoxic effects. Thus, this study aims to evaluate the mutagenicity of multi-walled carbon nanotubes (MWCNTs) functionalized in somatic cells of Drosophila melanogaster, using the somatic mutation and recombination test (SMART). This assay detects the loss of heterozygosity of marker genes expressed phenotypically on the wings of the fly. Larvae of three days were used, resulting from ST cross, with basal levels of the cytochrome P450 and larvae of high metabolic bioactivity capacity (HB cross). They were treated with different concentrations of MWCNTs functionalized. The MH descendants, analyzed in both ST and HB crosses, had no significant effects on the frequency of mutant. Based on the results and on the experimental conditions mentioned in this study, it was concluded that MWCNTs were not mutagenic in D. melanogaster.