Genes and Environment
Online ISSN : 1880-7062
Print ISSN : 1880-7046
28 巻 , 2 号
選択された号の論文の6件中1~6を表示しています
REVIEWS
  • Kiyoshi Fukuhara
    2006 年 28 巻 2 号 p. 41-47
    発行日: 2006年
    公開日: 2006/06/22
    ジャーナル フリー
    The protective role of antioxidants against free-radical associated diseases has been widely studied, leading to the development of new types of antioxidants to remove reactive oxygen species such as O2•- and OH. We synthesized a new type of synthetic antioxidant in which the catechol (B ring) and chroman moieties (AC ring) within the (+)-catechin (CA) structure were constrained to be planar. As compared with CA, planar catechin (PCA) showed strong radical scavenging activities towards both galvinoxyl and cumylperoxyl radicals. Reduced prooxidant activity was also observed, consistent with the dianion form of PCA being weaker at generating O2•- than the dianion form of CA. PCA completely inhibited DNA-strand scission induced by the Fenton reaction, whereas CA exhibited not only antioxidant properties but also prooxidant properties consistent with enhanced DNA strand cleavage. As compared with hydrophilic CA, the lipophilicity of PCA due to its planarity may aid in penetration of these antioxidant molecules past the cell membrane. Further development of planar PCA may be a favorable approach towards new clinically useful antioxidants for the treatment of free-radical associated diseases.
  • Toshinori Suzuki
    2006 年 28 巻 2 号 p. 48-55
    発行日: 2006年
    公開日: 2006/06/22
    ジャーナル フリー
    The incidence of cancer can be decreased by avoiding the intake of mutagens and carcinogens; however, cancer is also induced by endogenous factors. Water is the most essential substance for life, but causes DNA damage via the release of purine nucleobases from DNA, termed depurination, and the hydrolysis of amino groups of nucleobases, termed deamination. Nitric oxide and hypochlorous acid, essential compounds in the host defense system, are formed by specific enzymes and kill invading microorganisms. Nitric oxide reacts with nucleobases resulting in deamination products as well as hydrolysis. Recently, two novel products were identified in the reaction of nucleobases with nitric oxide. Hypochlorous acid reacts with nucleobases resulting in various products. In addition, several products including novel compounds have been identified in the reaction of hypochlorous acid with guanine. When DNA replication occurs without complete repair, these lesions cause mutations in cellular DNA, and accumulation of these mutations may cause cancer. Thus, we should consider water, nitric oxide, and hypochlorous acid in the human body as endogenous cancer risk factors. This review describes DNA damage and subsequent mutations caused by water, nitric oxide, and hypochlorous acid.
REGULAR ARTICLES
  • Toshihiro Ohta, Shin-ichi Tokishita, Kayo Mochizuki, Jun Kawase, Masah ...
    2006 年 28 巻 2 号 p. 56-61
    発行日: 2006年
    公開日: 2006/06/22
    ジャーナル フリー
    Thermus thermophilus is an aerobic, extremely thermophilic eubacterium that grows optimally at 70-75°C. Phylogenetically there is a close relationship between T. thermophilus and Deinococcus radiodurans, an extraordinary radiation-resistant bacterium. In contrast to the D. radiodurans, DNA repair and mutagenesis in T. thermophilus have not been investigated intensively. DNA repair and related mutagenesis at high temperature are particularly interesting because the frequency of DNA damage, such as deamination, depurination, and single strand breaks, is expected to be greatly increased. We disrupted the uvrA gene for subunit A of excinuclease ABC and uvdE gene for probable UV endonuclease by inserting the thermostable kanamycin-resistant gene (HTK) or orotate phosphoribosyltransferase (pyrE) gene. A uvrA mutant showed moderate sensitivity to UV-irradiation, while a uvdE mutant was not UV sensitive. A uvdE uvrA double mutant was highly sensitive to UV-irradiation compared with a uvrA mutant, indicating that UV endonuclease, a uvdE gene product, plays an important role in repair of UV-induced DNA damages. On the other hand, no obvious UV-induced mutations were observed when it was assayed by His+ reversion. It has been reported that T. thermophilus HB27 does not have an SOS response system, because no genes homologous to umuD, umuC, and lexA were found. In the absence of error-prone translesion DNA polymerases in T. thermophilus, mutations would not occur at the site of pyrimidine dimers
  • Takeshi Hirano, Kazuaki Kawai, Yuko Ootsuyama, Hiroshi Kasai
    2006 年 28 巻 2 号 p. 62-67
    発行日: 2006年
    公開日: 2006/06/22
    ジャーナル フリー
    Our previous work demonstrated that arsenic compounds increased 8-hydroxyguanine (8-OH-Gua) in the DNA of cultured human cells (A549) and reduced the endonuclease nicking activity for 8-OH-Gua, suggesting that arsenic compound-induced carcinogenesis was the consequence of the inhibition of DNA repair. However, the exact mechanism by which the repair systems were disturbed was unknown. To elucidate the mechanism, we analyzed mouse 8-oxoguanine DNA glycosylase 1 (mOGG1) expression in mouse nonparenchymal liver cells, NCTC, treated with arsenic compounds (arsenic trioxide, sodium arsenite, and sodium hydrogen arsenate). We detected a cleaved form of mOGG1 (35 kDa) in addition to normal mOGG1 (type 1a, 38 kDa) in NCTC treated with arsenic compounds. These results are similar to our previous results which showed that fragmentation of mOGG1 by etoposide was related to caspase-dependent apoptosis, and was accompanied by increased 8-OH-Gua accumulation. Taken together, our results suggested that arsenic compounds might increase 8-OH-Gua accumulation by inhibiting 8-OH-Gua repair, due to mOGG1 cleavage.
  • Li Zhan, Masamitsu Honma, Li Wang, Makoto Hayashi, De-Sheng Wu, Li-Shi ...
    2006 年 28 巻 2 号 p. 68-73
    発行日: 2006年
    公開日: 2006/06/22
    ジャーナル フリー
    The water pollution of toxic cyanobacteria (blue-green algae) is causing a serious public health problem in many parts of the world. Microcystin-LR (MCLR) is a potent cyclic heptapeptidic hepatotoxin produced by the cyanobacterium Microcystis aeruginosa. MCLR presents acute and chronic hazards to human health and has been linked to primary liver cancer in humans chronically exposed to this peptide toxin through drinking water. To assess the in vivo mutagenecity of MCLR, the λ/lacZ transgenic mice (MutaTMMouse) were treated with MCLR (1 mg/kg per week x 4) and examined for mutant frequencies (MFs) in the lacZ and cII genes of liver and lungs. Micronucleus induction in peripheral blood cells was also assessed. Co-mutagenic effect of MCLR was studied in combination with N-nitrosodiethylamine (DEN). MCLR did not increase either MFs of the target genes in liver and lungs or micronucleus frequency in the peripheral blood cells of the λ/lacZ transgenic mouse. While DEN treatment increased MFs significantly, the co-administration of MCLR did not potentiate its mutagenicity. We conclude that pure MCLR has no in vivo mutagenicity as it failed to induce gene mutation and micronucleus in transgenic mouse. Its tumor promoting effect is independent of its interaction to DNA.
SHORT COMMUNICATION
  • Kazuo Negishi, Shoichi Higashi, Takanori Nakamura, Chie Otsuka, Masaka ...
    2006 年 28 巻 2 号 p. 74-76
    発行日: 2006年
    公開日: 2006/06/22
    ジャーナル フリー
    The mechanisms of the toxic effects of UVA (320-400 nm) irradiation remain unclear. The actions of monochromatic longer wavelength UVA, in particular, have been difficult to analyze because of a lack of a powerful light source; however, a UVA laser that can be used for biological studies was recently developed. In the current studies, we examined the effects of 364-nm irradiation on yeast cells using a potent UVA laser. We found that, when irradiated under aerobic conditions, yeast cells lacking Ogg1 glycosylase were more sensitive than those with Ogg1. The ability of the 364-nm light to kill the yeast cells was almost eliminated by purging with argon gas. The mutagenic effects of the UVA irradiation did not appear to be enhanced by a lack of Ogg1. These results indicate the killing of yeast cells by 364-nm UVA may be dependent on oxidation and may involve DNA lesions that can be repaired by Ogg1.
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