著者

祖父尼 俊雄 能美 健彦 太田 敏博 林 真

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.61-73, 2005-07-31

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The concept of a "biological threshold" is attracting interest as an evaluation criterion for the mutagenic activity of DNA-targeting mutagens. In this context, the concept is defined as "a concentration of a chemical which does not produce any damage through its inability to perform the necessary biochemical reactions, even though present at the target in finite amount". To clarify whether this criterion is indeed applicable to DNA-targeting mutagens, we re-evaluated the reverse mutation assay data using DNA repair-deficient bacterial strains, such as S. typhimurium strains lacking the O^6-methylguanine DNA methyltransferase genes (ada_<ST> and ogt_<ST>), the nucleotide excision repair gene (uvrB) or the 8-hydroxyguanine DNA glycosylase gene (mutM_<ST>), and E. coli strains lacking the nucleotide excision repair gene (uvrA). Mutagenic responses of 20 test chemicals including alkylating and non-alkylating agents were compared between the repair-deficient and their wild-type strains. All the alkylating agents, such as MNNG, ENNG, EMS, ENU, DMN and DEN, exhibited more sensible mutagenic responses in strains YG7108 (Δada_<ST>, Δogt_<ST>) and YG7113 (same as YG7108 but containing the plasmid pKM101) than in the parental strains TA1535 and TA100 (same as TA1535 but containing the pKM101), respectively. Upon applying MNNG, YG7108 showed about 2-100 fold increase in the number of His^+ revertants above the spontaneous level over the range of 0.00025-0.25μg/plate, whereas TA1535 did not show any significant increase in the number of His^+ revertants over the same dose range. On TA1535, an increasing tendency of the number of revertants was observed at 0.5μg/plate or above. This indicates an approximate 2,000-fold difference at the mutagenic concentration level between the wild-type and the repair-deficient strains. Other alkylating agents also showed significant differences in mutagenic responses between YG7108 and TA1535, or between YG7113 and TA100 respectively, with some variations among test chemicals. On the other hand, non-alkylating agents, such as 4-NQO, AF-2, 2-NF and MX, did not show any differences in the dose-response relationships between YG7113 and TA100. When non-alkylating agents, such as 4-NQO, 2-NF and MX were applied to TA1535 (ΔuvrB), TA1538 (ΔuvrB) and WP2uvrA (ΔuvrA), clearly different mutagenic responses, i.e. about 30- to 60-fold, were observed between the repair-deficient and the parental strains (TA1975, TA1978 and WP2, respectively). 4-NQO showed different mutagenic responses between YG3002 (ΔmutM_<ST>) and TA1975 (about 10-fold), though the application of other oxidative agents such as hydrogen peroxide resulted in less than 10-fold differences. The present results indicate that the wild-type strains having normal repair capacity show no gene mutation induction at the concentrations at which gene mutations are clearly induced in the repair-deficient strains through DNA damage. Thus, the present results suggest the existence of a "biological threshold" below which no mutagenic response is induced by DNA-targeting mutagenic substances.

著者

大下 美雪 佐々木 有 関橋 薫 津田 修治 高沢 博修 宇野 芳文

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.29, 2000-10-24

著者

中西 真

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.2, pp.117-121, 2004 (Released:2005-12-21)

参考文献数

11

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Chk1 is required for arrest of the mammalian cell cycle before mitosis in response to DNA damage or replication block. It is also implicated in regulation of cell cycle progression because it is essential for embryonic cell viability. With the use of mouse embryonic stem cells conditionally deficient in Chk1, we now show that this kinase is indispensable for the timing of mitotic initiation. Chk1 deficiency resulted in premature onset of mitosis through reduction of Cdc2 phosphorylation on Tyr15 as a result of increased Cdc25 activity and decreased Wee1 activity. Our results suggest that Chk1 regulates Cdc2 to establish proper timing of mitotic initiation during the mammalian embryonic cell cycle.

著者

菊池 康基

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.1, pp.51-57, 2004 (Released:2005-12-13)

参考文献数

63

著者

坂本,豊

出版者

日本環境変異原学会

雑誌

環境変異原研究

巻号頁・発行日

vol.20, no.3, 1998-10-31

著者

田辺 秀之

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.1, pp.11-22, 2003 (Released:2005-08-19)

参考文献数

97

被引用文献数

1 1

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The individual chromosomes in animal and plant interphase cell nuclei are discretely highly compartmentalized called “chromosome territories” that are visualized by 3D-FISH techniques. The chromosome territories are mutually exclusive without mixing each other, formed in essential components of the higher order chromatin architecture. Here I reviewed historical aspects of studies on the chromosome territory and recent advancement of studies on the chromosome positioning in relation to nuclear architecture. Chromosome positioning in the interphase cell nuclei has been investigated with regard to the following two aspects : radial positioning or relative positioning. It has been generally considered that the former radial positioning of a given chromosome territory is correlated with its size, its gene-density, and replication timing, namely comprehended as non-random distribution. From a series of 3D-FISH studies on the primate and chicken cell nuclei, the topology of the radial positioning of human chromosomes 18 and 19 homologs shows highly evolutionarily conserved during the evolution, but its functional significance is still within the speculation. On the other hand, the relative positioning has much affects to the translocation frequencies between adjacent two chromosomes, that was experimentally indicated by the mouse lymphoma cell nuclei, but in human lymphocytes the majority of reports suggested the random organization without particular patterns except for some clusters formed between homologous chromosomes. In future studies higher order nuclear architecture in relation to chromosome territory will be more elucidated by 3D-FISH techniques combined with living cell (in vivo) approaches by means of visualizing various nuclear molecules.

著者

川端 留美 岡田 浩史 吉村 宏美 近藤 卓也 田中 剛太郎

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.33, 2004-11-30

著者

近藤 宗平

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.27, 1998

著者

北上,茂樹

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.36, 2007-11-10

著者

北上 茂樹 夏井 俊介 奥野 祥治 小田 美光 宇都宮 洋才 赤澤 真一

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.36, 2007

著者

尾後,早耶佳

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

林 哲也

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.117-118, 2005 (Released:2005-12-26)

参考文献数

5

著者

中川 宗洋

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.2, pp.3-4, 2004-09-30

著者

石館 基

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.21, no.1, pp.53-81, 1999

著者

Tohru Shibuya Yukiharu Horiya

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.33, no.2, pp.34-42, 2011 (Released:2011-05-25)

参考文献数

93

被引用文献数

4

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Epigenetics (EG) is a highly regulated biochemical mechanism underlying the expression of genes related to development and cellular differentiation that is disrupted by environmental stressors including chemicals and radiation. Studies of these phenomena are known as environmental epigenetics (EEG). Regulation of gene expression by the epigenetic mechanism is deeply involved in the developmental stages of animals and humans. EEG is, therefore, very important in the field of toxicology because it deals with the state of gene expression in all types of somatic and germ cells disrupted by environmental chemicals. We propose here an “Embryo-originated Epigenetic Toxicology Method (EEGT)”. In this method embryonic somatic and germ cells are treated with test substances and various toxicological phenomena in whole bodies are examined. Observations on transgenerational effects are also important in this method. This new method could unite various toxicological phenomena based on EEG.

著者

佐々木 蓉子 高木 岬 関本 征史 遠藤 治

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.44, 2015-11-24

著者

本郷 有克 若栗 忍 石川 陽一 梅田 誠 田中 憲穂

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.33, 2004-11-30

著者

尾崎 依里奈 川崎 祐也 河井 一明 藤川 和男

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.42, 2013-10-30

著者

平井 裕子 児玉 喜明 森脇 真一 野田 朝男 CULLINGS Harry 児玉 和紀 馬淵 清彦 KRAEMER Kenneth LAND Charles 中村 典

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.36, 2007-11-10

著者

祖父尼 俊雄 能美 健彦 太田 敏博 林 真

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.61-73, 2005 (Released:2005-12-26)

参考文献数

23

被引用文献数

9 9 1

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The concept of a “biological threshold” is attracting interest as an evaluation criterion for the mutagenic activity of DNA-targeting mutagens. In this context, the concept is defined as “a concentration of a chemical which does not produce any damage through its inability to perform the necessary biochemical reactions, even though present at the target in finite amount”. To clarify whether this criterion is indeed applicable to DNA-targeting mutagens, we re-evaluated the reverse mutation assay data using DNA repair-deficient bacterial strains, such as S. typhimurium strains lacking the O6-methylguanine DNA methyltransferase genes (adaST and ogtST), the nucleotide excision repair gene (uvrB) or the 8-hydroxyguanine DNA glycosylase gene (mutMST), and E. coli strains lacking the nucleotide excision repair gene (uvrA). Mutagenic responses of 20 test chemicals including alkylating and non-alkylating agents were compared between the repair-deficient and their wild-type strains.All the alkylating agents, such as MNNG, ENNG, EMS, ENU, DMN and DEN, exhibited more sensible mutagenic responses in strains YG7108 (ΔadaST, ΔogtST) and YG7113 (same as YG7108 but containing the plasmid pKM101) than in the parental strains TA1535 and TA100 (same as TA1535 but containing the pKM101), respectively. Upon applying MNNG, YG7108 showed about 2-100 fold increase in the number of His+ revertants above the spontaneous level over the range of 0.00025-0.25 μg/plate, whereas TA1535 did not show any significant increase in the number of His+ revertants over the same dose range. On TA1535, an increasing tendency of the number of revertants was observed at 0.5 μg/plate or above. This indicates an approximate 2,000-fold difference at the mutagenic concentration level between the wild-type and the repairdeficient strains. Other alkylating agents also showed significant differences in mutagenic responses between YG7108 and TA1535, or between YG7113 and TA100 respectively, with some variations among test chemicals. On the other hand, non-alkylating agents, such as 4-NQO, AF-2, 2-NF and MX, did not show any differences in the dose-response relationships between YG7113 and TA100. When non-alkylating agents, such as 4-NQO, 2-NF and MX were applied to TA1535 (ΔuvrB), TA1538 (ΔuvrB) and WP2uvrA (ΔuvrA), clearly different mutagenic responses, i.e. about 30- to 60-fold, were observed between the repair-deficient and the parental strains (TA1975, TA1978 and WP2, respectively). 4-NQO showed different mutagenic responses between YG3002 (ΔmutMST) and TA1975 (about 10-fold), though the application of other oxidative agents such as hydrogen peroxide resulted in less than 10-fold differences. The present results indicate that the wild-type strains having normal repair capacity show no gene mutation induction at the concentrations at which gene mutations are clearly induced in the repair-deficient strains through DNA damage. Thus, the present results suggest the existence of a “biological threshold” below which no mutagenic response is induced by DNA-targeting mutagenic substances.