Environmental Mutagen Research最新文献

{"title":"Antimutagenicity of 3-allyl-5-substituted 2-thiohydantoins derived from allyl isothiocyanate and amino acids in Salmonella assay","authors":"A. Takahashi, H. Matsuoka, Y. Uda","doi":"10.3123/JEMS.26.1","DOIUrl":"https://doi.org/10.3123/JEMS.26.1","url":null,"abstract":"Nine 3-allyl-5-substituted 2-thiohydantoins (ATH-amino acids) which were prepared from allyl isothiocyanate (AITC) and amino acids were studied for their antimutagenic activities against 2-amino-3-methylimidazo [4,5-f] quinoline (IQ) and 4-nitroquinoline 1-oxide (4-NQO) using the Ames assay. The assay against IQ was performed on S. typhimurium TA98 in the presence of a metabolic activation system (S9 mix) and that against 4-NQO was carried out on S.typhimurium TA100 in the absence of S9 mix. When ATH-amino acids except for that prepared from AITC and aspartic acid were simultaneously treated with the bacterial strain and IQ, an inhibition of IQ mutagenicity was observed. Also, all ATH-amino acids showed a suppressive effect on 4-NQO mutagenicity when the bacterial strain was incubated in the presence of both 4-NQO and ATH-amino acids. In contrast, little antimutagenic effect was observed when ATH-amino acids were added to the bacterial strains which has been pretreated with a mixture of IQ and S9 mix or only 4-NQO. These results suggest that ATH-amino acids are capable of acting as inhibitors of the S9 mix-mediated activation of IQ and/or as modulators of the direct-acting mutagen, 4-NQO.","PeriodicalId":394432,"journal":{"name":"Environmental Mutagen Research","volume":"s4-1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2004-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126850563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reversible phenotype and a lack of direct link to immortalization of Syrian hamster embryonic cells obtained from so-called transformed colonies","authors":"H. Tsuda","doi":"10.3123/JEMS.25.159","DOIUrl":"https://doi.org/10.3123/JEMS.25.159","url":null,"abstract":"The short-term colony transformation assay employing Syrian hamster embryonic (SHE) cells has been widely used as a simple method for detection of chemical and physical carcinogens. However, little investigation has been done on the biological properties of the early transformed colony (ETC: colony characterized by piling up and criss-cross pattern of growth) itself. This study was performed to examine the properties of these colonies. Secondary or tertiary cultures of SHE cells were treated with benzo[a]pyrene or N-methyl-N’-nitro-N-nitrosoguanidine. In total, 37 ETCs and 17 normal colonies (NCs) were cloned and analyzed. Obtained results were as follows: (1) Stability of transformed morphology; immediately after cloning, the cells from 3/37 of the ETCs maintained their transformed phenotype, but all cells from other ETCs (34/37) showed flat or well-oriented morphology. Thus, the “transformed” morphology of more than 90% of the ETCs was reversible. (2) Chromosome abnormality; 3/15 of the clones from ETCs were hypo diploid or tetraploid, while the others (12/15) were normal diploid immediately after cloning. (3) Immortalization; up to about one month after cloning, most of the clones (from transformed or normal colonies) could be subcultured at 1:2 or 1:4 split ratio per week, but thereafter all the clones ceased growing. After about a one month or longer latency, 6/37 of the clones from ETCs and 4/17 of the clones from NCs restarted growing and acquired immortality. That is, there was no significant difference in the frequency of immortalization between ETCs and NCs. Thus, from the present experiment, there was no direct evidence that ETC correlates to acquisition of immortality or tumorigenesis. Further experiments (e.g. comparison of gene expression profiles between cells from transformed and normal colonies using microarray) would be required to give a logical meaning to this short-term transformation assay.","PeriodicalId":394432,"journal":{"name":"Environmental Mutagen Research","volume":"9 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2003-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126831166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of in vitro exposure time on comet assay results","authors":"Kaoru Sekihashi, H. Saitoh, A. Saga, K. Hori, M. Nakagawa, M. Miyagawa, Y. Sasaki","doi":"10.3123/JEMS.25.83","DOIUrl":"https://doi.org/10.3123/JEMS.25.83","url":null,"abstract":"Some mutagens are inactivated rapidly by components included in culture media, especially by serum. Long incubation periods may not be appropriate for the comet assay because DNA lesions may be repaired during the time that mutagens are inactivated, leading to false negative results. We questioned how the exposure period of Chinese hamster ovary cells to 8 unstable mutagens affected outcome of the assay.Although the longest biological half-life of the test mutagens was 1.98 h, four were positive following 0.5—24 h incubations while other four were positive only when the incubation period was ≤ 4 h, suggesting that the DNA damage was repaired and the mutagens were inactivated. The rapid inactivation of mutagens in the medium did not affect whether the outcome of the comet assay was positive or negative when cells were exposed for 1—4 h. Based on these results, we concluded that long exposure should not be employed for the compounds that are unstable in culture media, and appropriate incubation time should be determined for them individually.","PeriodicalId":394432,"journal":{"name":"Environmental Mutagen Research","volume":"9 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2003-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129096330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved method for preparation of S9-activated heterocyclic amines","authors":"S. Arimoto-Kobayashi, H. Hayatsu","doi":"10.3123/JEMS.25.77","DOIUrl":"https://doi.org/10.3123/JEMS.25.77","url":null,"abstract":"We investigated improved methods for the preparation of metabolically activated forms of heterocyclic amines referred to as ‘activated heterocyclic amines’. We also described the influence of pH on the metabolic activation of Trp-P-2, and on the stability and mutagenicity of the activated form of Trp-P-2.","PeriodicalId":394432,"journal":{"name":"Environmental Mutagen Research","volume":"45 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2003-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116088742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the VitotoxTM test as a high-throughput genotoxicity assay","authors":"S. Muto, H. Baba, Y. Uno","doi":"10.3123/JEMS.25.69","DOIUrl":"https://doi.org/10.3123/JEMS.25.69","url":null,"abstract":"The VitotoxTM test is a high-throughput bacterial genotoxicity test based on the SOS DNA-repair system induced by genotoxic compounds. Two genetically engineered Salmonella typhimurium strains are used in this system, TA104recN2-4 (Genox strain), that contains the bacterial luciferase (lux) operon (luxCDABE) under transcriptional control of recN promoter, and TA104 pr1 (Cytox strain), that constitutively expresses lux operon.The performance of the VitotoxTM test was evaluated with 33 known Ames positive chemicals, 26 known Ames negatives and 18 drug candidates developed at Mitsubishi Pharma Corporation. Ten compounds had inconclusive results because they caused SOS-independent enhancement of light emission. Among 49 known chemicals with conclusive results, 89% of the Ames positive compounds were detected as positive (genotoxic) with the VitotoxTM test, and all of the Ames negative compounds were detected as negative. There was a 94% concordance between the Ames test results and the VitotoxTM test results.In a practical validation study using 18 drug candidates developed at Mitsubishi Pharma Corporation, 7 of 8 Ames positive compounds were detected as genotoxic and all of the Ames negative compounds gave negative results with the VitotoxTM test. The concordance between the VitotoxTM test results and the Ames test results for 18 drug candidates was 94% (17/18). Moreover, the VitotoxTM test required a smaller sample quantity than the Ames test to detect genotoxicity.The present results indicate that the VitotoxTM test is useful for rapid screening of large numbers of chemicals when only a small quantity of a chemical is available.","PeriodicalId":394432,"journal":{"name":"Environmental Mutagen Research","volume":"121 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2003-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131254061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in the chemical induction of micronuclei in the rat.","authors":"S. Hamada, Kazuo Nakajima, C. Namiki, T. Serikawa, M. Hayashi","doi":"10.3123/JEMS.25.33","DOIUrl":"https://doi.org/10.3123/JEMS.25.33","url":null,"abstract":"The micronucleus assay was conducted with 7 chemicals (2-acetylaminofluoren [2-AAF], 1-β-D-arabinofuranosylcytosine [Ara-C], colchicine, cyclophosphamide [CP], methyl methanesulfonate [MMS], potassium bromate [KBrO3], urethane) in male and female rats to determine whether the results varied with sex. Each chemical was administered twice orally, 24 h apart, to 5 rats in each of 3 dosage groups and collected bone marrow and peripheral blood 24 h later. Sex differences were observed in micronucleus induction in both polychromatic erythrocytes (bone marrow) and reticulocytes (peripheral blood), which we attributed to a sex difference in hematopoiesis. In spite of those differences, both sexes showed positive responses. We concluded that the rat is suitable for the micronucleus assay regardless of sex.","PeriodicalId":394432,"journal":{"name":"Environmental Mutagen Research","volume":"519 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2003-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123119828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Achievements of the late Kiyoshi Tutikawa, a mouse geneticist","authors":"Y. Kikuchi","doi":"10.3123/JEMS.26.51","DOIUrl":"https://doi.org/10.3123/JEMS.26.51","url":null,"abstract":"1)マウスの系統維持と日本産マウスの遺伝学的研究 第二次大戦後の混乱がまだ治まらない 1951年に,先 生が北大から遺伝研に赴任する際,恩師の牧野佐二郎北 大教授より移送を託されたネズミ達と共に貨物列車に乗 り込み,札幌から三島まで,数日かけて運んだときの苦 労話を,雑誌「自然」に書かれている(土川,1978b). これが先生のマウス研究の原点といっても過言ではなか ろう. 当時の遺伝研には,小熊 捍所長や駒井 卓先生など, わが国の遺伝学の泰斗がおられた.また,実験動物の質 向上の重要性を認識された小熊,駒井両先生をはじめ, 中原和郎,安東洪次,田嶋嘉雄などの諸先生から,親し く教えを受けたことが,土川先生の遺伝研における研究 に大きな影響をもたらしたことは,想像にかたくない. 1953年には文部省科研費によって,わが国初の近代的 な飼育室が遺伝研に設立され,先生は Jackson記念研究 所に留学される 1956年まで,その管理・運営に当たら れた.","PeriodicalId":394432,"journal":{"name":"Environmental Mutagen Research","volume":"71 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128717304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A review of my research on environmental mutagens","authors":"H. Nishioka","doi":"10.3123/JEMS.27.29","DOIUrl":"https://doi.org/10.3123/JEMS.27.29","url":null,"abstract":"私は京都大学医学部薬学科(現薬学部)を卒業し(1957 年),大阪市立衛生研究所(現大阪市環境科学研究所)に 就職した.細菌学の研究室に配属され,ここでバクテリ アやウイルスなどの細菌学の技術を身につけた.当時, 細菌の形質転換,形質導入,接合などのメカニズムや DNAの分子構造の解明など,分子生物学と呼ばれたこ の分野は目覚しい展開をみせ,私は興味を駆り立てられ た.当時の私の研究テーマは,抗生物質などに対する細 菌の耐性獲得のメカニズムであったが,このとき,微生 物の突然変異の研究に魅せられ,これが私の一生のテー マになった. 1961年,東京工業大学原子炉工学研究所に助手とし て転職し,各種放射線による大腸菌の突然変異誘導メカ ニズムの研究を開始した.機会を得て,1967年から 1972年まで米国に留学し,当時,紫外線による突然変 異研究で,目覚しい業績を上げていたC. ダウドニー博 士(A. アインシュタイン研究所)やW. ハーム教授(テキ サス大学)らの研究室で,主として紫外線による大腸菌 の突然変異誘導のメカニズムを研究した. 当時,紫外線(UVC)によるDNAの主要な損傷は,ピ リミジンダイマーであること,これらの損傷はいくつか のメカニズムで修復されること,修復は正確なものと, 不正確なものがあって,不正確な修復によっても突然変 異が誘導されることがあることがわかっていた.これら のメカニズム研究は謎解きともいえるもので,私はその 面白さに没頭した. 1973年,帰国して同志社大学に赴任し,工学部教授 として,生化学の研究と教育に携わることになった.私 立大学なので,卒業論文作成のために,毎年,多数の学 生が私の研究室に配属され,卒論生の数だけ研究テーマ を必要とした.当時,環境問題が社会的関心事となり始 めた頃であり,化学系の学生に,環境変異原を研究させ るのは都合のよいことであった.この頃に設立された, 日本環境変異原研究会(現日本環境変異原学会)は,私た ちの研究を発表するいい機会となった. 第 4回日本環境変異原研究会(京都,1975年)は,私が 勤務する同志社大学で行われた.この当時,変異原とい う言葉は社会には全く知られていなかったが,ある事件 のために,変異原がマスコミを通じて,一般に広まるこ とになった.当時,食品添加物としてわが国だけが採用 していた殺菌剤AF2(フリルフラマイド)に強い変異原性 が発見され,これがマスコミに報道され,社会は一挙に","PeriodicalId":394432,"journal":{"name":"Environmental Mutagen Research","volume":"48 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116260600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tandem repeat DNA: applications in mutation analysis","authors":"C. Yauk, Aris A. Polyzos","doi":"10.3123/JEMS.27.93","DOIUrl":"https://doi.org/10.3123/JEMS.27.93","url":null,"abstract":"Non-coding tandem repeat DNA sequences have high rates of mutation that facilitate the measurement of induced mutation in small sample sizes. It has been suggested that these loci may be useful biomarkers for heritable genetic mutation induced by exposure to genotoxic agents. Significant induction of mutation is quantifiable in the germline of mice exposed to mutagens. The primary focus of this work has been on exposure to radiation. The data suggest that meiosis or DNA replication/repair may be required for induction of mutation in the germline at tandem repeats. Mutations arise via indirect mechanisms rather than by direct damage to the repeat locus itself, therefore reflecting genomic instability rather than targeted DNA damage. These markers have also been used to measure induced germline mutations in animals exposed to ambient levels of urban air pollution. The mutagenicity is associated with particulate matter in the air but the exact chemical nature of the mutagens is unknown. Lack of knowledge of the relationship between ESTR instability and gene mutation, and lack of understanding of the mechanisms resulting in instability prevent inference on the health-related implications of induced tandem repeat mutation. We have developed single-molecule PCR approaches to study ESTR instability in vitro. This method circumvents the requirement of sub-cloning and allows for many more individual ESTR alleles to be examined. These types of laboratory-based experiments will be crucial in clarifying the types of chemicals that can generate tandem repeat instability and thereby provide insight into the mechanisms of action and the putative mutagens found in complex environmental matrices.","PeriodicalId":394432,"journal":{"name":"Environmental Mutagen Research","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133892093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What is required of JEMS","authors":"M. Hayashi","doi":"10.3123/jems.25.1","DOIUrl":"https://doi.org/10.3123/jems.25.1","url":null,"abstract":"The constitution of the Japanese Environmental Mutagen Society (JEMS) says, “The society aims to encourage basic research on mutagens in humans, other organisms, and the environment, especially mutagens that affect public health. It also aims to further good communication and the transfer of research techniques in related subjects” (Chapter 4). I believe that JEMS should follow these written objectives of the society precisely and honestly. The main theme of the 31st JEMS annual meting is, “Challenges to Internationalization and Humanization”, and it is the current requirement to the society that member want. On the matter of “Internationalization”, we held the 8th ICEM at Shizuoka last year under the most difficult circumstances and had great success, providing evidence that JEMS is effective internationally. We also played an important role in having our research in this field reflected in regulation considered in international harmonizing activities (i.e., International Workshop on Genotoxicity Testing). On the other hand, to take care global problems, e.g., air and water, international cooperation is important. Our society, however, has made little effort to cooperate with the Asian EM societies with except for a few individuals. JEMS should seek ways to collaborate on problems we share with these countries. We could possibly be a hub for communication between societies that are located in Asian countries. In an effort to do that, we organized the “Asian Environmental Mutagen Societies Forum”, hoping that it would eventually head to an Asian Association of Environmental Mutagen Societies.The topic of “Humanization” is a most important one. The ultimate goal of our field is the maintaining the highest possible quality of life (QOL), and that includes maintains the environment that affects our QOL directly or indirectly in good condition. For this purpose our society should focus more on human risk assessment, including exposure assessments of environmental mutagens, and molecular epidemiology.In addition to the main issues mentioned above, our society should orient our research more to the genome than to the detection of environmental mutagens. Also, I think that the society should contribute to regulatory requirement. This includes organizing validation studies of novel technology and establishing strategies on how to evaluate and interpret test data.From the administrative viewpoint, the organization of JEMS should be more transparent and the responsibilities of the executive and the council should be clarified. Moreover, we need to establish a mechanism for gathering opinions from the membership. On the web, we have started to improve our Home Page and mailing system to permit better communication between the executive board and society members and also among members.Lastly, I would like to mention the society’s important research activities. Our sub-organizations include the Mammalian Mutagenicity Study Group (MMS), the Bacterial Mutagenic","PeriodicalId":394432,"journal":{"name":"Environmental Mutagen Research","volume":"46 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133544167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}