著者

山田 雅巳

出版者

日本環境変異原学会

雑誌

環境変異原研究 (ISSN:09100865)

巻号頁・発行日

vol.25, no.2, pp.87-92, 2003 (Released:2005-08-19)

参考文献数

8

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Gene disruption methods are useful to construct bacteria lacking a specific gene especially when a gene’s function is unknown. In the 1980s, complementation techniques were used as the first step in cloning a gene. With the advances made through genome projects, gene identification and cloning have allowed easier construction of deficient bacterial strains with cloned genes. In this report, I describe three methods of disrupting specific genes on chromosomes in a strain of interest, namely linear transformation, preligation and the ‘one-step’ method. Moreover, several genetic techniques which are necessary for conducting these methods are also reviewed.

著者

鈴木 孝昌

出版者

日本環境変異原学会

雑誌

環境変異原研究 (ISSN:09100865)

巻号頁・発行日

vol.25, no.3, pp.181-185, 2003 (Released:2005-08-19)

参考文献数

5

被引用文献数

1

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Has mutation research contributed sufficiently to the genetic risk assessment of chemicals? The answer may be “No”. Although it has contributed much to predict carcinogenicity, how much benefit has exposure prevention of those mutagens brought to public health? It is suggested that the proportion of human carcinogenesis related to environmental chemicals is less than 10%. The main causes for cancer are tobacco smoking, diet, and aging. As genetic toxicologists, we have become too satisfied with a qualitative evaluation of mutation assay results and try to detect as many “carcinogens” as possible. This approach ignores the quantitative evaluation, which is more important in risk assessment. Many “carcinogens”, especially socalled non-genotoxic carcinogens, do not cause cancer at the human exposure level. The “genotoxic non-carcinogens”, if they exist, may be more important because cancer is not the only toxicological outcome of genotoxicity. We should pay more attention to heritable genetic effects of chemicals. An increasing incidence of smoking among young women alerts us to investigate the genetic effects of smoking in their progeny.The paradigm shift from hazard identification to risk assessment is important in mutation research. In this regard, quantitative, mechanism-based, and humanized mutation assays are required.

著者

奥山 治美

出版者

日本環境変異原学会

雑誌

環境変異原研究 (ISSN:09100865)

巻号頁・発行日

vol.25, no.2, pp.147-157, 2003 (Released:2005-08-19)

参考文献数

87

被引用文献数

2 4

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Substances causing persistent inflammation (asbestos, viruses and pathogens) are often carcinogenic even if they are not directly mutagenic. Reactive oxygen species from inflammatory cells injure DNA and are cell-proliferative leading to accelerated carcinogenesis. Lipid mediators in the linoleic acid (LA) cascade through arachidonic acid (n-6) and some cytokines form amplification cascades to stimulate these processes, whereas the fatty acids of n-3 type competitively suppress the LA cascade and carcinogenesis. This interpretation is consistent with the observations that (1) dietary oils with low n-6/n-3 ratios are suppressive compared with high-LA oils, (2) inhibitors of the LA cascade are suppressive, and (3) manipulations to knockout genes related to the LA cascade are suppressive for carcinogenesis. On the other hand, many kinds of genes are affected differently by the chain length and unsaturation of fatty acids regardless of the n-6 or n-3 type. Saturates, monounsaturates and LA up-regulate cholesterol synthesis leading to enhanced prenylation of oncogene products, cell-proliferation and carcinogenesis. Dietary cholesterol and high tissue cholesterol levels feedback suppress cholesterol synthesis and cell-proliferative stimuli, which partly accounts for epidemiological observations that cancer mortality is lower in the group with higher cholesterol level. For the cancers, the incidence of which is high in the US and has been increasing rapidly in Japan, reducing the intake of LA to half while maintaining those of n-3 fatty acids and animal fats at the levels of average Japanese is recommended.

著者

Suminori Akiba

出版者

日本環境変異原学会

雑誌

Genes and Environment (ISSN:18807046)

巻号頁・発行日

vol.35, no.3, pp.80-87, 2013 (Released:2013-09-03)

参考文献数

52

被引用文献数

1 5

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Whether chronic exposure has an cancer risk per dose different from that of acute exposure is a topic of debate. This paper discusses the effect of dose rate on the strength of relationship between cancer risk and external exposure to low-LET (Linear Energy Transfer) ionizing radiation (such as X-rays and gamma rays), by reviewing important epidemiological studies. The study of atomic-bomb survivors, who had acute exposure mainly to low-LET ionizing radiation, has shown that the excess relative risk per gray (ERR/Gy) of leukemia increases in a linear-quadratic manner with an increase of radiation dose. The estimate of ERR/Gy for medium-high dose ranges was shown to be approximately two-fold larger than that for a low-dose range in the atomic-bomb survivor study. The estimate of ERR/Gy associated with acute exposure appears to be larger than those obtained from the studies of low-dose-rate exposure. On the other hand, the risk of solid cancer (or all cancers excluding leukemia) showed a linear dose-response relationship. Regarding the risk modification by dose rates, lower dose-rate exposure to high LET radiation is suspected to be associated with a larger risk. In the case of low-LET exposure, however, the cancer incidence study of residents in high natural background radiation areas of Karunagappally Taluk in Kerala State, India suggests that the ERR per dose for solid cancer after chronic radiation exposure is significantly lower than that associated with acute exposure such as that experienced by atomic-bomb survivors.

著者

鈴木 啓司 児玉 靖司 渡邉 正己

出版者

日本環境変異原学会

雑誌

環境変異原研究 (ISSN:09100865)

巻号頁・発行日

vol.27, no.2, pp.111-115, 2005 (Released:2005-12-26)

参考文献数

29

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Ionizing radiation induces genomic instability, which is transmitted through many generations after irradiation in the progeny of surviving cells. We have hypothesized that radiation-induced large deletion causes potentially unstable chromosome regions, which are involved in delayed induction of radiation-induced genomic instability. Using phosphorylation-specific antibodies against ATM and histone H2AX, whose phosphorylation is induced by DNA double strand breaks, we detected delayed induction of phosphorylated ATM and H2AX foci in the progeny of X-ray-surviving cells, which indicated delayed induction of DNA double strand breaks. Furthermore, we found delayed chromosomal instability in X chromosomes in clones which contain large deletion involving the HPRT loci. It is suggested that large deletion involving —Mb region causes unstable chromatin structure, and it results in delayed rearrangement of chromosomes involved. These findings provide the possibility that manifestation of radiation-induced genomic instability results from delayed DNA breaks, i.e., the breaks lead to delayed chromosome rearrangements, delayed cell death etc., many generations after irradiation.

著者

中村 宜督

出版者

日本環境変異原学会

雑誌

環境変異原研究 (ISSN:09100865)

巻号頁・発行日

vol.26, no.3, pp.253-258, 2004 (Released:2005-12-24)

参考文献数

25

被引用文献数

1 1

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An important group of compounds that have a chemopreventive property is organosulfur compounds such as isothiocyanates. In the present study, we clarified the molecular mechanism underlying the relationship between benzyl isothiocyanate (BITC)-induced cell cycle arrest and apoptosis. The exposure of the cultured cells to BITC resulted in the inhibition of the G2/M progression that coincided with apoptosis induction. An experiment using phase-specific synchronized cells demonstrated that the G2/M phase-arrested cells are more sensitive to undergoing apoptotic stimulation by BITC than the cells in other phases. We identified phosphorylated Bcl-2 as a key molecule linking the p38 MAPK-dependent cell cycle arrest with JNK activation by BITC. We also found that BITC induced a cytotoxic effect more preferentially in the proliferating normal human colon epithelial cells than the quiescent cells. Moreover, down-regulation of p53 resulted in the enhancement of susceptibility to undergoing apoptotic stimulation by BITC. These findings suggested that p53 might play a negative regulating role in BITC-induced apoptosis. In conclusion, the results from this study provided biological evidence that BITC has a potential to induce apoptosis selectively in p53-mutated proliferating pre-cancerous cells.

著者

東海林 克彦

出版者

日本環境変異原学会

雑誌

環境変異原研究 = Genes and environment : the official journal of the Japanese Environmental Mutagen Society (ISSN:18807046)

巻号頁・発行日

vol.27, no.2, pp.121-124, 2005-07-31

参考文献数

7

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This article aims to introduce the outline of issue and phenomena of welfare of laboratory animals which is enacted in Law for Welfare and Proper Management of Animals, and to clarify the difference of conception and method between welfare of laboratory animals and experiment using laboratory animals, in anticipation of contributing to its improvement in practice.

著者

鈴木 孝昌 小原 有弘 ラマダン アリ 菊池 裕 本間 正充 林 真

出版者

日本環境変異原学会

雑誌

日本環境変異原学会大会プログラム・要旨集

巻号頁・発行日

no.38, 2009-11-06

著者

Yun-Shan Li Ming-Fen Song Hiroshi Kasai Kazuaki Kawai

出版者

日本環境変異原学会

雑誌

Genes and Environment (ISSN:18807046)

巻号頁・発行日

vol.35, no.3, pp.88-92, 2013 (Released:2013-09-03)

参考文献数

16

被引用文献数

1 10

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Human epidemiological studies have revealed significant increases in the cancer incidence rates by exposure to 100 mSv or higher doses of ionizing radiation. However, the relationship between lower doses of ionizing radiation and cancer incidence is still unclear. In general, oxidative DNA damage is closely related to cancer generation. We studied the oxidative DNA damage elicited by low dose ionizing irradiation. The γ-ray irradiation of a deoxyguanosine solution caused a linear increase in the 8-hydroxydeoxyguanosine (8-OHdG) levels, in the range of 20-300 mGy. Thus, 8-OHdG seems to be a good marker of the oxidative DNA damage caused by ionizing radiation. In contrast, in the case of the whole body X-ray irradiation of mice, the 8-OHdG levels in liver DNA and urine increased from about 500 and 200 mGy, respectively. These results indicate that living organisms have a defense mechanism against the oxidative damage caused by ionizing radiation. Considering the 8-OHdG levels as an ionizing radiation effect marker for living organisms, a threshold level of irradiation seems to exist for oxidative damage and tumorigenesis. Furthermore, diet imbalances increased radiation damage. Lifestyle may affect the radiation hazard.

著者

福島 昭治 鰐渕 英機 森村 圭一朗 魏 民

出版者

日本環境変異原学会

雑誌

環境変異原研究 (ISSN:09100865)

巻号頁・発行日

vol.27, no.2, pp.75-79, 2005 (Released:2005-12-26)

参考文献数

11

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Until recently it has been generally considered that genotoxic carcinogens have no threshold in exerting their potential for cancer induction. However, the non-threshold theory can be challenged with regard to assessment of cancer risk to humans. In the present study we show that food-related genotoxic hepatocarcinogens, heterocyclic amines and N-nitroso compounds at low doses do not induce preneoplastic lesions and cancer-related markers in rat medium-term carcinogenicity bioassay. The results imply existence of a threshold, at least practical one, for carcinogenicities of genotoxic carcinogens.

著者

東海林 克彦

出版者

日本環境変異原学会

雑誌

環境変異原研究 (ISSN:09100865)

巻号頁・発行日

vol.27, no.2, pp.121-124, 2005 (Released:2005-12-26)

参考文献数

7

---

This article aims to introduce the outline of issue and phenomena of welfare of laboratory animals which is enacted in Law for Welfare and Proper Management of Animals, and to clarify the difference of conception and method between welfare of laboratory animals and experiment using laboratory animals, in anticipation of contributing to its improvement in practice.

著者

鈴木,孝昌

出版者

日本環境変異原学会

雑誌

日本環境変異原学会大会プログラム・要旨集

巻号頁・発行日

no.38, 2009-11-06

著者

Jun Takada

出版者

日本環境変異原学会

雑誌

Genes and Environment (ISSN:18807046)

巻号頁・発行日

vol.35, no.3, pp.69-72, 2013 (Released:2013-09-03)

参考文献数

10

被引用文献数

1

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Radiation hygiene survey has been conducted in the East Japan earthquake area, about Fukushima Dai-Ichi nuclear power station disaster caused by tsunami on March 11, 2011. Our surveys revealed that a public annual dose was 10 mSv following the disaster and health hazards should not be concluded by the methods of in situ dose evaluation. This study has been focused on internal dosimetries of iodine-131 in thyroid and of cesium-134, 137 in whole body. Further, we continuously have been studying radiation hygiene on cattle livestock in Namie town located within 20 km zone around the Fukushima Daiichi nuclear power station, and found no problem for the recovery.

著者

Shizuyo Sutou

出版者

日本環境変異原学会

雑誌

Genes and Environment (ISSN:18807046)

巻号頁・発行日

pp.2014.017, (Released:2014-06-07)

参考文献数

22

被引用文献数

1 1 1

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Bipedalism paved the way to delivery of immature babies and development of the brain after birth. This communication presents the argument that hairlessness allowed hominins to access fire through wildfires, which occurred frequently after a climate shift from a wet to a dry environment 2.5 million years ago (Ma). Initially, naked hominins approached fire for warming, but soon must have come across burnt animals in the aftermath of wildfires. They learned the taste of burnt meat, which must have been a driving force compelling them to become meat-eaters. Hominins must have learned gradually how to control fire and how to repel hairy animals that abhor fire. Because they could neither run fast nor have muscles sufficiently strong to compete with large carnivores' fangs and claws, they chose not to be hunters but robbers. When they found that a carnivore had killed a prey animal, they approached the hungry predator and repulsed it using fire and stones, then claiming the prey intact. This is the core of the human robber hypothesis. The timing of global cooling, the appearance of savannahs, the appearance of transitional humans, decline of large predators, the manufacture of stone tools, and the start of cooking largely coincide at 2.5 Ma. They also smoked out animals from their dens or caves, and robbed them of shelter and territory. Cooked meat is both tasty and easily digested, providing hominins with rich nutrients sufficient to enlarge the brain, while most large carnivores were forced to extinction. Consequently, the use of fire, facilitated by hairlessness, must have played important roles in protecting hominins from cold, in repelling predators, in robbing large carnivores of prey and dwellings, and in providing the brain with nutrients for strong growth into adolescence. Development of the eccrine glands is also discussed as a result of hairlessness.

著者

高野 泰樹 宮田 昌明 山添 康

出版者

日本環境変異原学会

雑誌

日本環境変異原学会大会プログラム・要旨集

巻号頁・発行日

no.31, 2002-10-31

著者

宮田 昌明 高野 泰樹 山添 康

出版者

日本環境変異原学会

雑誌

環境変異原研究 (ISSN:09100865)

巻号頁・発行日

vol.26, no.3, pp.247-251, 2004 (Released:2005-12-24)

参考文献数

23

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Co-intake of grapefruit juice with drugs results in a substantial increase in oral drug bioavailability. In contrast, DNA damage in target organ induced by a food-derived carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), was reduced in rats by grapefruit juice intake. Aflatoxin B1-induced DNA damage was also suppressed in rats treated with grapefruit juice and an ethyl acetate extract of grapefruit juice. A significant decrease in hepatic CYP3A content, but not in CYP1A, CYP2C, glutathione S-transferase and microsomal epoxide hydrolase contents was observed in rats after grapefruit juice intake. No significant differences in the portal blood and liver concentrations of aflatoxin B1, nor in blood concentration of PhIP, were observed between control rats and rats ingesting grapefruit juice. Thus, grapefruit juice intake causes suppression of carcinogen-induced DNA damage at least in part through decreased metabolic activation in rat liver.

著者

Takehiko Nohmi Masamitsu Honma Masami Yamada Kenichi Masumura Manabu Yasui Katsuyoshi Horibata Shoji Fukushima

出版者

日本環境変異原学会

雑誌

Genes and Environment (ISSN:18807046)

巻号頁・発行日

vol.34, no.4, pp.141-145, 2012 (Released:2012-11-27)

著者

小川 祥 渡辺 貴志 庄司 さやか 降旗 千惠

出版者

日本環境変異原学会

雑誌

日本環境変異原学会大会プログラム・要旨集

巻号頁・発行日

no.43, 2014

著者

Shizuyo Sutou Takashi Egawa Hiroki Mori Hiroaki Aso

出版者

日本環境変異原学会

雑誌

Genes and Environment (ISSN:18807046)

巻号頁・発行日

vol.35, no.3, pp.73-79, 2013 (Released:2013-09-03)

参考文献数

6

被引用文献数

2

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The March 11 earthquake and tsunami crippled the Fukushima Daiichi Nuclear Power Plant of Tokyo Electric Power Company. Consequently, wide areas were contaminated with radioactive substances. The evacuation zone was set as the area within a 20 km radius from the power plant. People who lived in that zone were forced to evacuate immediately. Fukushima Prefectural Disaster Headquarters (FPDH) and the Japanese Governmental Disaster Headquarters (JGDH) planned to let them return to their homes temporarily and asked for help from related organizations, one of which is the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan. The ministry asked all Japanese universities and colleges to take part in screening radioactivity of the temporal returnees from the areas, with aids of the temporal returning program. We applied to the screening activities and measured radioactivity of the returnees at Bajikoen Off-site Center on July 14-17, 2011, and at Kawauchi Gymnasium or Hirono Central Gymnasium Off-site Center on July 23-25, 2011, in Fukushima Prefecture. During these periods, 4009 returnees in all were screened at these three Off-site Centers. None was found to be contaminated with radioactivity over 13,000 cpm. Before the returnee screening program, emergency screening had been conducted soon after the disaster. In all, 33,598 people out of 78,000 evacuees (43%) were screened during March 12-December 7, 2011, during which 3,686 volunteers were recruited by MEXT for the screening program. This is a tiny fraction of the temporal returning program. FPDH reported that 102 people were contaminated with more than 100,000 cpm out of 259,108 people generally screened from March 13, 2011-October 10, 2012. The 102 were detected only in the screening in March in 2011. No hazardous effect, however, was detected among them, so far. Screening is still underway. The present article was compiled to record aspects of the large scale radioactivity monitoring program planned by FPDH and JGDH.

著者

及川 伸二 村田 真理子 平工 雄介 川西 正祐 Shinji Oikawa Mariko Murata Yusuke Hiraku Shosuke Kawanishi 三重大学医学部衛生学教室 三重大学医学部衛生学教室 三重大学医学部衛生学教室 三重大学医学部衛生学教室 Department of Hygiene Mie University School of Medicine Department of Hygiene Mie University School of Medicine Department of Hygiene Mie University School of Medicine Department of Hygiene Mie University School of Medicine

出版者

日本環境変異原学会

雑誌

環境変異原研究 = Environmental mutagen research communication (ISSN:09100865)

巻号頁・発行日

vol.23, no.3, pp.207-213, 2001-12-22

参考文献数

33

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Reactive oxygen species are capable of causing damage to various cellular constituents, such as DNA, proteins and lipids, leading to carcinogenesis, aging and a number of diseases. We have investigated the sequence specificity of oxidative stress-mediated DNA damage by using ^<32>P-labeled DNA fragments obtained from the human c-Ha-ras-1, p53 and p16 genes. The sequence specificity of DNA damage plays the key role in the mutagenic process, and affects the mutation frequency. Therefore, investigation on sequence specificity of DNA damage would provide clues on the biological significance of DNA damage which in turn may be beneficial for cancer prevention strategy. Here we discuss the mechanisms and sequence specificity of DNA damage caused by various environmental chemicals and UVA-activated photosensitizers in relation to carcinogenesis and aging.