Genes and Environment
Online ISSN : 1880-7062
Print ISSN : 1880-7046
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33 巻 , 3 号
選択された号の論文の7件中1~7を表示しています
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REVIEW
  • Lynnette R. Ferguson
    原稿種別: Review
    33 巻 (2011) 3 号 p. 71-78
    公開日: 2011/08/12
    ジャーナル フリー
    An anti-mutagen is any substance that reduces the rate of spontaneous mutations or counteracts or reverses the action of a mutagen, or any technique that protects cells against the effects of mutagens. Studies as early as the 1940s reported on substances that delayed detection of radiation-induced mutations, or reduced the appearance of mutations induced by chemicals such as acridine orange. However, a far more sophisticated range of anti-mutagens is now being identified. Mutagen scavengers act through absorption onto a larger molecule that is readily excreted. Good examples are provided by dietary fibre sources, such as wheat bran, or the planar molecule, chlorophyll and its stabilised derivative, chlorophyllin. Mutagens may be actively extruded from human cells through the action of one or more of a series of ATP-binding cassette (ABC) drug transporter proteins, including the multidrug resistance proteins (P-glycoproteins), multidrug resistance-associated proteins (MRP1-7) and the breast cancer resistance protein (BCRP). These proteins can affect the absorption, distribution and excretion of mutagens and carcinogens, as well as of their metabolites and conjugates. Even if the undesirable compound enters the cells, there are several mechanisms by which it may be prevented from interaction with DNA. Detoxification mechanisms are of increasing interest, especially those where transcription is regulated through the antioxidant response element (ARE), whose own transcription factor, Nrf2, is repressed under basal conditions. While much of the early literature on mutagenesis and carcinogenesis implicated exogenous chemicals, it is increasingly realised that unrepaired oxidative DNA lesions are important mutational precursors, and anti-oxidants represent an important class of anti-mutagens. It is also recognised that deficiency of certain micronutrients may lead to cell mutation, and that restoring nutrient balance is an important mechanism of anti-mutagenesis. An increasing number of studies focus on DNA repair and stress responses as novel mechanisms of anti-mutagenesis.
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REGULAR ARTICLE
  • Takanori Nakamura, Megumi Nakai, Kaikou Ookubo, Yoshihisa Kitamura, No ...
    原稿種別: Regular article
    33 巻 (2011) 3 号 p. 81-88
    公開日: 2011/08/12
    ジャーナル フリー
    The anti-genotoxicity effect of aqueous extracts of Connarus ruber cortex was studied in cultured human cells and mice. Connarus extract decreased bi-nuclei cells with micronuclei (MNBNC) significantly in NER-proficient WTK1 cells that were exposed to MNU, MMC, or UVC and in NER-deficient XPL3KA cells (that is, in XP-C) that were exposed to MNU or MMC, but not UVC. The genotoxicity-suppressing effect was further studied by the comet assay. Connarus extract decreased DNA migration significantly in WTK1 cells that were exposed to MNU or UVC and in XPL3KA cells that were exposed to MNU but not UVC. In WTK1 cells, in contrast, DNA migration increased with the extract in the presence of DNA repair inhibitors (araC and HU), suggesting that the anti-genotoxic potential is due to an enhanced incision step of global genome repair (GGR) subpathways in NER. Chemical analysis revealed that the extract contains epicatechine, one of the anti-mutagenic components contained in green tea. Connarus extract fractions that decreased UVC-induced DNA migration were those not to contain epicatechine and they were different from those that decreased MNU-induced DNA migration, suggesting that some anti-mutagenic components other than epicatechine might be contained in Connarus extract and that a number of anti-genotoxic components with different modes of anti-genotoxicity are contained in Connarus extract. The anti-clastogenic effect of Connarus extracts was examined in mice using a micronucleus assay. When mice received ≦2000 mg/kg Connarus extract by oral gavage at the same time as intraperitoneal injection of MMC, a decrease in the frequency of micronucleated reticulocytes was observed. This decrease was not due to a delay in the maturation of micronucleated reticulocytes.
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  • Masaru Fujiwara, Yuko Hamatake, Sakae Arimoto, Keinosuke Okamoto, Tosh ...
    原稿種別: Regular article
    33 巻 (2011) 3 号 p. 89-95
    公開日: 2011/08/12
    ジャーナル フリー
    Recently, we reported experimental evidence to support the notion that in Drosophila melanogaster, urate is involved in defense against toxic effects of environmental cigarette smoke (ECS). To obtain further information pertaining to the defense mechanisms involving urate and other antioxidants, the present study measured the levels of urate, its precursors and glutathione, and SOD activity in larval flies of wild-type strains (Oregon-R and Canton-S) and two urate-null mutant strains (ma-l and ry1) following exposure to ECS for various durations. In both wild type strains, unlike the case in either of the mutant strains, the urate level significantly increased above the basal level in a manner dependent on the duration of ECS exposure. Similar increases in the level of urate precursors were found in Canton-S and in both of the urate-null strains. There was a slight increase in glutathione level above the control level following ECS exposure for a short time, followed by an exposure-dependent decrease to less than 60% of the control level within the exposure range used in all of the four strains. On the other hand, no appreciable change was found in the SOD activity prior to or following ECS exposure, irrespective of the strain examined. In terms of the survival of treated larvae to adulthood under the conditions used for the measurements of urate and others, it was found that wild-type strain Canton-S was as sensitive as the urate-null mutant strains and clearly more sensitive than wild-type strains Oregon-R and Hikone-R. This was so despite the fact that, compared with Oregon-R, Canton-S contained urate at relatively higher levels prior to and following ECS exposure, and that the glutathione levels in Canton-S prior to and following treatment were comparable with those in other strains. These results are discussed with respect to the involvement of urate and glutathione in defense against the toxicity of ECS and the possible existence of another defense mechanism which is deficient in the Canton-S strain.
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  • Hironao Takasawa, Kiyoshi Wako, Yukari Sato, Rie Takashima, Akiko Hatt ...
    原稿種別: Regular article
    33 巻 (2011) 3 号 p. 96-102
    公開日: 2011/08/12
    ジャーナル フリー
    The comet assay is widely used as an in vivo/in vitro genotoxicity test to detect initial DNA damage in a single cell. Air containing ions generated by electric discharge was examined in lung comet assays in rats and mice. Using whole-body inhalation, the animals were continuously exposed to the ionized air (abbreviated as IONA) for 48 h at the concentrations range 100−700×104 ions/cm3. Lung cell samples were prepared by mincing, and blood cells were also sampled and diluted with mincing buffer to confirm the results obtained with lung cells. Slide preparation and electrophoresis for the comet assay were conducted in accordance with the standard protocol (Version 14.2) provided by the Validation Management Team of the “International Validation Study of In Vivo Alkaline Comet Assay” controlled by the Japanese Center for the Validation of Alternative Methods (JaCVAM). Results of the lung comet assays in both rats and mice showed that the IONA exposure induced no significant differences in tail migration (tail length) or DNA-percentage in tail. In contrast, ethyl methanesulfonate used as the positive control gave clear positive responses in the assays. In the IONA-exposed groups, no abnormal changes were noted in clinical observations or body weight for rats or mice. Additionally, no IONA exposure-related abnormalities were detected in histopathological examinations in either species. Taken together, these results indicate that IONA has no potential to induce DNA damage in the lungs and has no effect on the general health conditions of animals, body weight or histopathology in the lungs under the conditions employed in this study.
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