Genes and Environment
Online ISSN : 1880-7062
Print ISSN : 1880-7046
28 巻 , 4 号
選択された号の論文の7件中1~7を表示しています
REVIEW
  • Yusuke Hiraku, Mariko Murata, Shosuke Kawanishi
    2006 年 28 巻 4 号 p. 127-140
    発行日: 2006年
    公開日: 2006/12/20
    ジャーナル フリー
    Dietary factors are implicated in approximately 35% of cancers attributed to environmental factors. Although an extremely wide variety of dietary factors are considered to contribute to carcinogenesis, its precise mechanism remains to be clarified. We focused on the role of oxidative DNA damage in carcinogenesis mediated by various dietary factors. We investigated the mechanism of oxidative DNA damage induced by a) amino acid metabolites, in relation to carcinogenesis caused by protein intake and amino acid imbalance, b) heterocyclic amines formed during cooking meat and fish, c) sugar and hyperglycemia-related aldehydes, d) carcinogens contained in fermented foods, such as urethane, e) phytoestrogens including soy isoflavones, f) carcinogens in edible plants, such as caffeic acid and isothiocyanate, g) food additives, such as potassium bromate and benzoyl peroxide. These dietary factors and their metabolites induced metal-mediated oxidative damage to DNA in human cultured cells and 32P-labeled DNA fragments obtained from human cancer-relevant genes. On the basis of our results, it is concluded that polycyclic compounds, such as heterocyclic amines, can cause oxidative DNA damage, although they appear to mainly form DNA adduct. On the other hand, monocyclic and aliphatic compounds, such as amino acid metabolites and urethane, may mainly cause oxidative DNA damage whereas they do not appear to form DNA adduct. Soy isoflavones may cause carcinogenesis through initiation via oxidative DNA damage caused by their metabolites and promotion via cell proliferation induced by themselves. In this review, we discuss the role of oxidative DNA damage as the common mechanism of dietary carcinogenesis.
COMMENTARY
  • Takeshi Morita, Makoto Hayashi, Kaoru Morikawa
    2006 年 28 巻 4 号 p. 141-152
    発行日: 2006年
    公開日: 2006/12/20
    ジャーナル フリー
    The Globally Harmonized System (GHS) on hazard classification and labeling of chemicals will be implemented globally by 2008. The GHS includes (a) harmonized criteria for classifying chemicals and chemical mixtures according to their health, environmental and physical hazards, and (b) harmonized hazard communication elements, including requirements for labeling and safety data sheets. Germ cell mutagenicity is included in the GHS health hazard classes in addition to carcinogenicity. This means increased significance for then results of genetic toxicology testing for the classification of chemicals. GHS requires the classification of chemicals if they are germ cell mutagens (categories 1A, 1B and 2) or not. Several classification systems for germ cell mutagens have been proposed in the EU, Germany, US, Canada, in advance of the adoption of the GHS. In this paper, these classification systems including GHS are introduced and summarized to provide the basis of the hazard classification of germ cell mutagens. Though the objectives, target audiences and criteria of these classification systems are different, the GHS will become standard for hazard classification. Hazard classification is a significant first step in risk communication. Further development of risk evaluation criteria and communication on germ cell mutagens is expected.
REGULAR ARTICLES
  • Ritsuo Arakawa, Mie Terao, Hiroe Hayashi, Hiroshi Kasai, Tomoe Negishi
    2006 年 28 巻 4 号 p. 153-159
    発行日: 2006年
    公開日: 2006/12/20
    ジャーナル フリー
    The sunlight that reaches the surface of the earth is composed of polychromatic light with wavelengths ranging from 290 nm to 2500 nm. Ultraviolet (UV) light is a component of sunlight that is harmful to organisms. Although it is known that sunlight induces photoproducts and harmful effects such as major DNA damage caused by UV light in the tissues of many species including human skin, it is not clear whether sunlight induces oxidative damage in organisms. In this study, we investigated whether sunlight causes oxidative damage in exposed organisms using Drosophila. Third instar larvae were exposed to sunlight for an evaluation of viability and 8-hydroxydeoxyguanosine (8-OHdG) content. Urate-null Drosophila mutant larvae (ry506), which are sensitive to active oxygen-producing agents, were more sensitive to sunlight lethality than the wild-type strain under limited conditions. This sunlight-induced toxicity in ry506 larvae was partially prevented by pretreatment of larvae with 400 mM uric acid. The level of 8-OHdG in DNA showed no significant increase in both strains. In contrast, sunlight was significantly mutagenic for all seasons as reported previously. These results suggest that sunlight is partly responsible for oxidative damage in Drosophila and that 8-OHdG-formation plays little or no role in sunlight-induced mutation and toxicity.
  • Kazuhiko Takahashi, Masaharu Asanoma, Satoshi Yoshida, Gao Ning, Haruy ...
    2006 年 28 巻 4 号 p. 160-166
    発行日: 2006年
    公開日: 2006/12/20
    ジャーナル フリー
    An organic extract from surface soil collected at a park in Nagoya, Aichi prefecture, which showed extremely high mutagenicity in Salmonella typhimurium TA98 in the absence of a mammalian metabolic system (S9 mix), was investigated to identify the major mutagens. A potent bacterial mutagen was isolated from the organic extract (1.03 g) of the soil sample (2.1 kg) by column chromatography. On the basis of mass spectra, the mutagen, which accounted for 8.8% of the mutagenicity of the soil extract, was thought to be a trinitrated polycyclic aromatic hydrocarbon with a molecular weight of m/z 337. The mutagen was synthesized from pyrene by nitration with nitric acid and was identified as 1,3,6-trinitropyrene (1,3,6-TNP) based on its 1H NMR spectrum. The mutagenicity of 1,3,6-TNP in an Ames assay using S. typhimurium was extremely high, in that it induced 65,500 revertants/nmol in TA98, without S9 mix. This level of activity was slightly lower than that of 1,6-dinitropyrene (DNP), 129,800 revertants/nmol, or 1,8-DNP, 217,000 revertants/nmol, but was greater than that of 1,3-DNP, 4,260 revertants/nmol. These results indicate that 1,3,6-TNP was one of the major mutagens in surface soil collected at a park in Nagoya city, and this is the first report on the detection of 1,3,6-TNP in surface soil.
  • Masanobu Kawanishi, Michiyo Sakamoto, Chiaki Shimohara, Takashi Yagi
    2006 年 28 巻 4 号 p. 167-172
    発行日: 2006年
    公開日: 2006/12/20
    ジャーナル フリー
    Polymorphism of the aryl hydrocarbon receptor (AhR) presumably induces genetic difference in the susceptibility of animals to aryl hydrocarbons. The activation of intracellular signaling following AhR binding to aryl hydrocarbons is highly correlated with the toxicity and carcinogenicity of these chemicals. Here we developed two reporter yeasts coexpressing AhR and AhR nuclear translocator (Arnt) proteins of a guinea pig and a Syrian hamster, known as the most sensitive and most resistant laboratory rodents to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), respectively. We previously constructed reporter yeasts expressing human and mouse AhR/Arnt. We conducted reporter assays to measure ligand activities of TCDD, 3-methylcholanthrene, β-naphthoflavone and indirubin in these yeasts. Ligand treatment induced a dose-dependent increase in β-galactosidase activity from a reporter plasmid in all 4 yeast strains. The assays showed that yeast expressing guinea pig AhR/Arnt is most sensitive and yeast expressing Syrian hamster AhR/Arnt is most insensitive to these ligands. The yeasts expressing human and mouse AhR/Arnt were in-between. These different ligand activities reflect the species specificity of AhR/Arnt, and may be related to the susceptibility of rodents to aryl hydrocarbons.
  • Tetsushi Watanabe, Tomohiro Hasei, Takeshi Ohe, Teruhisa Hirayama, Kei ...
    2006 年 28 巻 4 号 p. 173-180
    発行日: 2006年
    公開日: 2006/12/20
    ジャーナル フリー
    In a previous study, we found that water concentrate from the Waka River, which flows through an industrial area in Wakayama, Japan, showed significant mutagenicity in Salmonella typhimurium YG1024 without a mammalian metabolic system (S9 mix), and 4-amino-3,3′-dichloro-5,4′-dinitrobiphenyl (ADDB) was identified as a major direct-acting mutagenic constituent in the water concentrate. ADDB induced 428,000 revertants/μg in YG1024 without S9 mix, and this activity was 48 times as high as that with S9 mix. In this study, to clarify whether other mutagenic contaminants were present in the river, water concentrates were collected at three sites along the Waka River and examined for mutagenicity by the Ames test using YG1024 and YG1029 with and without S9 mix. All water concentrates showed potent mutagenicity in YG1024 with and/or without S9 mix. ADDB was detected in water concentrate that was extremely mutagenic without S9 mix. An indirect-acting mutagen, which accounted for more than 30% of the total mutagenicity of the water concentrates in YG1024 with S9 mix, was isolated from two extremely mutagenic water concentrates by HPLC separation. On the basis of spectral data and co-chromatography using authentic chemicals, this mutagen was identified as 3,3′-dichlorobenzidine (DCB). DCB showed strong mutagenicity in YG1024 with S9 mix, inducing 5,186 revertants/μg. DCB was detected in water concentrates collected on the other three sampling dates in the range from 15.8 to 28.5 μg/g of blue rayon. These results suggest that Waka River water might be continually contaminated with mutagens, and DCB was thought to be the major mutagenic constituent of the river water.
SHORT COMMUNICATION
  • Toshihiro Ohta
    2006 年 28 巻 4 号 p. 181-184
    発行日: 2006年
    公開日: 2006/12/20
    ジャーナル フリー
    The combined mutagenic effects of six heterocyclic amines (Trp-P-1, Trp-P-2, Glu-P-1, Glu-P-2, MeIQ, and IQ) at doses below the biological threshold level of each were investigated in the reverse mutation assay with Salmonella typhimurium. The lowest mutagenic doses of heterocyclic amines in TA1978P (hisD3052, rfa/pKM101) were 40 to 200 times the lowest mutagenic doses in TA98 (hisD3052, rfa, uvrB/pKM101), a strain deficient in nucleotide excision repair. The six heterocyclic amines were mixed at doses below the biological threshold that were mutagenic to TA98 but not to TA1978P. A significant increase in the number of revertants in TA1978P was observed with combined heterocyclic amines. The results suggest that DNA adduct formation at doses below the biological threshold level was additive, with the total amount reflecting the mutagenicity. We should consider the potential for additive effects of mutagens when we consider biological thresholds, because most of environmental mutagens exist in complex mixtures of chemicals.
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