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Sizuyo Sutou - One of the best experts on this subject based on the ideXlab platform.

  • The 10th anniversary of the publication of genes and environment: memoir of establishing the Japanese Environmental Mutagen society and a proposal for a new collaborative study on Mutagenic hormesis
    Genes and Environment, 2017
    Co-Authors: Sizuyo Sutou
    Abstract:

    The Japanese Environmental Mutagen Society (JEMS) was established in 1972 by 147 members, 11 of whom are still on the active list as of May 1, 2016. As one of them, I introduce some historic topics here. These include 1) establishment of JEMS, 2) the issue of 2-(2-furyl)-3-(3-nitro-2-furyl)acrylamide (AF-2), 3) the Mammalian Mutagenicity Study Group (MMS) and its achievements, and 4) the Collaborative Study Group of the Micronucleus Test (CSGMT) and its achievements. In addition to these historic matters, some of which are still ongoing, a new collaborative study is proposed on adaptive response or hormesis by Mutagens. There is a close relationship between Mutagens and carcinogens, the dose-response relationship of which has been thought to follow the linear no-threshold model (LNT). LNT was fabricated on the basis of Drosophila sperm experiments using high dose radiation delivered in a short period. The fallacious 60 years-old LNT is applied to cancer induction by radiation without solid data and then to cancer induction by carcinogens also without solid data. Therefore, even the smallest amount of carcinogens is postulated to be carcinogenic without thresholds now. Radiation hormesis is observed in a large variety of living organisms; radiation is beneficial at low doses, but hazardous at high doses. There is a threshold at the boundary between benefit and hazard. Hormesis denies LNT. Not a few papers report existence of chemical hormesis. If Mutagens and carcinogens show hormesis, the linear dose-response relationship in Mutagenesis and carcinogenesis is denied and thresholds can be introduced.

  • evaluation of the rodent micronucleus assay by a 28 day treatment protocol summary of the 13th collaborative study by the collaborative study group for the micronucleus test csgmt Environmental Mutagen society of japan jems mammalian Mutagenicity stu
    Environmental and Molecular Mutagenesis, 2001
    Co-Authors: Shuichi Hamada, Sizuyo Sutou, Takeshi Morita, Akihiro Wakata, Shougo Asanami, Satoko Hosoya, Shigenari Ozawa, Koji Kondo, Madoka Nakajima, Hiroyasu Shimada
    Abstract:

    To examine whether micronucleus tests can be incorporated into general toxicology assays, we performed micronucleus tests applying the treatment protocols typically used in such assays. In this 13th Collaborative Study of the CSGMT, both rats and mice were tested, although rats were used in the majority of the studies. Fifteen Mutagens were tested in rats, mainly by oral (p.o.) administration. Micronucleus induction was evaluated 2, 3, and 4 days, and 1, 2, 3, and 28 days after the beginning of the treatment in the peripheral blood, and at 28 days in the bone marrow. Of the 15 chemicals that induced micronuclei in rats in short-term assays, two chemicals (1,2-dimethylhydrazine.2HCl and mitomycin C) were negative in all our experiments, possibly because of insufficient dose levels. The remaining 13 were positive within the estimated dose range of a general toxicology assay, suggesting the possibility of integrating the micronucleus assay into general toxicology assays. Three patterns were observed in micronucleus induction during the period of repeated treatment: (1) gradual increases in micronucleus frequency with sequential doses, (2) a peak at 3-5 days followed by gradual decreases in micronucleus frequency with sequential doses, and (3) a rapid increase in micronucleus frequency followed by a plateau. We evaluated factors that might have been involved in those patterns, such as the spleen function, target organ exposure, extramedullary hematopoiesis, hypothermia, and hypoxia. Another factor we considered was dosage. Because the dosages employed in a general toxicity assay are usually lower than those used in short-term micronucleus assays, this discrepancy was considered the greatest potential problem for integrating the micronucleus assay into general toxicology assays. Our results indicate that the integration of the micronucleus assay into a 28-day toxicological assay is feasible. To serve this purpose, blood samples collected 4 days after the beginning of treatment and blood and bone marrow samples collected at autopsy should be examined. Furthermore, although it is recognized that mice may be suitable for performing independent micronucleus assays, we propose that rats can provide biologically important and relevant information regarding potential chemical Mutagens that can be evaluated under conditions used in the conduct of general toxicology studies.

  • in vivo rodent erythrocyte micronucleus assay ii some aspects of protocol design including repeated treatments integration with toxicity testing and automated scoring
    Environmental and Molecular Mutagenesis, 2000
    Co-Authors: Makoto Hayashi, Takeshi Morita, James T. Macgregor, Stephen D. Dertinger, D.g. Gatehouse, I D Adler, David H Blakey, G Krishna, Antonella Russo, Sizuyo Sutou
    Abstract:

    An expert working group on the in vivo micronucleus assay, formed as part of the International Workshop on Genotoxicity Test Procedures (IWGTP), discussed protocols for the conduct of established and proposed micronucleus assays at a meeting held March 25-26, 1999 in Washington, DC, in conjunction with the annual meeting of the Environmental Mutagen Society. The working group reached consensus on a number issues, including: (1) protocols using repeated dosing in mice and rats; (2) integration of the (rodent erythrocyte) micronucleus assay into general toxicology studies; (3) the possible omission of concurrently-treated positive control animals from the assay; (4) automation of micronucleus scoring by flow cytometry or image analysis; (5) criteria for regulatory acceptance; (6) detection of aneuploidy induction in the micronucleus assay; and (7) micronucleus assays in tissues (germ cells, other organs, neonatal tissue) other than bone marrow. This report summarizes the discussions and recommendations of this working group. In the classic rodent erythrocyte assay, treatment schedules using repeated dosing of mice or rats, and integration of assays using such schedules into short-term toxicology studies, were considered acceptable as long as certain study criteria were met. When the micronucleus assay is integrated into ongoing toxicology studies, relatively short-term repeated-dose studies should be used preferentially because there is not yet sufficient data to demonstrate that conservative dose selection in longer term studies (longer than 1 month) does not reduce the sensitivity of the assay. Additional validation data are needed to resolve this point. In studies with mice, either bone marrow or blood was considered acceptable as the tissue for assessing micronucleus induction, provided that the absence of spleen function has been verified in the animal strains used. In studies with rats, the principal endpoint should be the frequency of micronucleated immature erythrocytes in bone marrow, although scoring of peripheral blood samples gives important supplementary data about the time course of micronucleus induction. When dose concentration and stability are verified appropriately, concurrent treatment with a positive control agent is not necessary. Control of staining and scoring procedures can be obtained by including appropriate reference samples that have been obtained from a separate experiment. For studies in rats or mice, treatment/sampling regimens should include treatment at intervals of no more than 24 hr (unless the test article has a half-life of more than 24 hr) with sampling of bone marrow or blood, respectively, within 24 or 40 hr after the last treatment. The use of a DNA specific stain is recommended for the identification of micronuclei, especially for studies in the rat. In the case of a negative assay result with a non-toxic test article, it is desirable that systemic exposure to the test article is demonstrated. The group concluded that successful application of automated scoring by both flow cytometry and image analysis had been achieved, and defined criteria that should be met if automated scoring is employed. It was not felt appropriate to attempt to define specific recommended protocols for automated scoring at the present time. Other issues reviewed and discussed by the working group included micronucleus assays that have been developed in a number of tissues other than bone marrow. The group felt that these assays were useful research tools that could also be used to elucidate mechanisms in certain regulatory situations, but that these assays had not yet been standardized and validated for routine regulatory application.

  • achievements by csgmt jems mms the collaborative study group for the micronucleus test in the mammalian Mutagenesis study group of the Environmental Mutagen society of japan
    Mutation Research\ reviews in Genetic Toxicology, 1996
    Co-Authors: Sizuyo Sutou
    Abstract:

    The Collaborative Study Group for the Micronucleus Test (CSGMT) is one of the task groups in the Mammalian Mutagenesis Study Group (MMS) of the Environmental Mutagen Society of Japan (JEMS). It was established in 1982 and has made efforts to understand what the micronucleus test is, what are the advantages and disadvantages of the test as an in vivo detection system for Mutagens/carcinogens, and to establish a standard protocol applicable to numerous chemicals. Members of the CSGMT have published more than 75 papers as part of collaborative studies and have contributed to the understanding of the nature of the micronucleus test and to setting guidelines for testing of medicinal and other chemicals. The CSGMT held some workshops to share up-to-date knowledge and techniques on the micronucleus test. Through workshops and collaborative studies, the CSGMT contributed to the maintaining of a high standard of knowledge and techniques among Japanese researchers of the micronucleus test. This paper reviews achievements made by the CSGMT until now.

  • Achievements by CSGMT/JEMS·MMS: the Collaborative Study Group for the Micronucleus Test in the Mammalian Mutagenesis Study Group of the Environmental Mutagen Society of Japan
    Mutation research, 1996
    Co-Authors: Sizuyo Sutou
    Abstract:

    The Collaborative Study Group for the Micronucleus Test (CSGMT) is one of the task groups in the Mammalian Mutagenesis Study Group (MMS) of the Environmental Mutagen Society of Japan (JEMS). It was established in 1982 and has made efforts to understand what the micronucleus test is, what are the advantages and disadvantages of the test as an in vivo detection system for Mutagens/carcinogens, and to establish a standard protocol applicable to numerous chemicals. Members of the CSGMT have published more than 75 papers as part of collaborative studies and have contributed to the understanding of the nature of the micronucleus test and to setting guidelines for testing of medicinal and other chemicals. The CSGMT held some workshops to share up-to-date knowledge and techniques on the micronucleus test. Through workshops and collaborative studies, the CSGMT contributed to the maintaining of a high standard of knowledge and techniques among Japanese researchers of the micronucleus test. This paper reviews achievements made by the CSGMT until now.

Shuichi Hamada - One of the best experts on this subject based on the ideXlab platform.

  • evaluation of the repeated dose liver micronucleus assay using n nitrosomorpholine in young adult rats report on collaborative study by the collaborative study group for the micronucleus test csgmt japanese Environmental Mutagen society jems mammalia
    Mutation Research-genetic Toxicology and Environmental Mutagenesis, 2015
    Co-Authors: Aya Hayashi, Mizuki Kosaka, Aoi Kimura, Yumi Wako, Kazufumi Kawasako, Shuichi Hamada
    Abstract:

    The present study was conducted to evaluate the suitability of a repeated-dose liver micronucleus (LMN) assay in young adult rats as a collaborative study by the Mammalian Mutagenicity study (MMS) group. All procedures were performed in accordance with the standard protocols of the MMS Group. Six-week-old male Crl:CD(SD) rats (5 animals/group) received oral doses of the hepatocarcinogen N-nitrosomorpholine (NMOR) at 0 (control), 5, 10, and 30mg/kg/day (10mL/kg) for 14 days. Control animals received vehicle (water). Hepatocytes were collected from the liver 24h after the last dose, and the number of micronucleated hepatocytes (MNHEPs) was determined by microscopy. The number of micronucleated immature erythrocytes (MNIMEs) in the femoral bone marrow was also determined. The liver was examined using histopathologic methods after formalin fixation. The results showed statistically significant and dose-dependent increases in the number of MNHEPs in the liver at doses of 10mg/kg and greater when compared with the vehicle control. However, no significant increase was noted in the number of MNIMEs in the bone marrow at doses of up to 30mg/kg. Histopathology of the liver revealed hypertrophy and single cell necrosis of hepatocytes at doses of 5mg/kg and above. These results showed that the induction of micronuclei by NMOR was detected by the repeated-dose LMN assay, but not by the repeated-dose bone marrow micronucleus assay.

  • evaluation of the repeated dose liver and gastrointestinal tract micronucleus assays with 22 chemicals using young adult rats summary of the collaborative study by the collaborative study group for the micronucleus test csgmt the japanese environment
    Mutation Research-genetic Toxicology and Environmental Mutagenesis, 2015
    Co-Authors: Shuichi Hamada, Yasushi Shimada, Tadashi Imamura, Wakako Ohyama, Rie Takashima, Keisuke Shimada, Kazumi Matsumoto, Satoru Kawakami, Shoji Matsumura, Hisakazu Sanada
    Abstract:

    Abstract The repeated-dose liver micronucleus (RDLMN) assay using young adult rats has the potential to detect hepatocarcinogens. We conducted a collaborative study to assess the performance of this assay and to evaluate the possibility of integrating it into general toxicological studies. Twenty-four testing laboratories belonging to the Mammalian Mutagenicity Study Group, a subgroup of the Japanese Environmental Mutagen Society, participated in this trial. Twenty-two model chemicals, including some hepatocarcinogens, were tested in 14- and/or 28-day RDLMN assays. As a result, 14 out of the 16 hepatocarcinogens were positive, including 9 genotoxic hepatocarcinogens, which were reported negative in the bone marrow/peripheral blood micronucleus (MN) assay by a single treatment. These outcomes show the high sensitivity of the RDLMN assay to hepatocarcinogens. Regarding the specificity, 4 out of the 6 non-liver targeted genotoxic carcinogens gave negative responses. This shows the high organ specificity of the RDLMN assay. In addition to the RDLMN assay, we simultaneously conducted gastrointestinal tract MN assays using 6 of the above carcinogens as an optional trial of the collaborative study. The MN assay using the glandular stomach, which is the first contact site of the test chemical when administered by oral gavage, was able to detect chromosomal aberrations with 3 test chemicals including a stomach-targeted carcinogen. The treatment regime was the 14- and/or 28-day repeated-dose, and the regime is sufficiently promising to incorporate these methods into repeated-dose toxicological studies. The outcomes of our collaborative study indicated that the new techniques to detect chromosomal aberrations in vivo in several tissues worked successfully.

  • evaluation of the rodent micronucleus assay by a 28 day treatment protocol summary of the 13th collaborative study by the collaborative study group for the micronucleus test csgmt Environmental Mutagen society of japan jems mammalian Mutagenicity stu
    Environmental and Molecular Mutagenesis, 2001
    Co-Authors: Shuichi Hamada, Sizuyo Sutou, Takeshi Morita, Akihiro Wakata, Shougo Asanami, Satoko Hosoya, Shigenari Ozawa, Koji Kondo, Madoka Nakajima, Hiroyasu Shimada
    Abstract:

    To examine whether micronucleus tests can be incorporated into general toxicology assays, we performed micronucleus tests applying the treatment protocols typically used in such assays. In this 13th Collaborative Study of the CSGMT, both rats and mice were tested, although rats were used in the majority of the studies. Fifteen Mutagens were tested in rats, mainly by oral (p.o.) administration. Micronucleus induction was evaluated 2, 3, and 4 days, and 1, 2, 3, and 28 days after the beginning of the treatment in the peripheral blood, and at 28 days in the bone marrow. Of the 15 chemicals that induced micronuclei in rats in short-term assays, two chemicals (1,2-dimethylhydrazine.2HCl and mitomycin C) were negative in all our experiments, possibly because of insufficient dose levels. The remaining 13 were positive within the estimated dose range of a general toxicology assay, suggesting the possibility of integrating the micronucleus assay into general toxicology assays. Three patterns were observed in micronucleus induction during the period of repeated treatment: (1) gradual increases in micronucleus frequency with sequential doses, (2) a peak at 3-5 days followed by gradual decreases in micronucleus frequency with sequential doses, and (3) a rapid increase in micronucleus frequency followed by a plateau. We evaluated factors that might have been involved in those patterns, such as the spleen function, target organ exposure, extramedullary hematopoiesis, hypothermia, and hypoxia. Another factor we considered was dosage. Because the dosages employed in a general toxicity assay are usually lower than those used in short-term micronucleus assays, this discrepancy was considered the greatest potential problem for integrating the micronucleus assay into general toxicology assays. Our results indicate that the integration of the micronucleus assay into a 28-day toxicological assay is feasible. To serve this purpose, blood samples collected 4 days after the beginning of treatment and blood and bone marrow samples collected at autopsy should be examined. Furthermore, although it is recognized that mice may be suitable for performing independent micronucleus assays, we propose that rats can provide biologically important and relevant information regarding potential chemical Mutagens that can be evaluated under conditions used in the conduct of general toxicology studies.

Yasushi Shimada - One of the best experts on this subject based on the ideXlab platform.

  • evaluation of the repeated dose liver and gastrointestinal tract micronucleus assays with 22 chemicals using young adult rats summary of the collaborative study by the collaborative study group for the micronucleus test csgmt the japanese environment
    Mutation Research-genetic Toxicology and Environmental Mutagenesis, 2015
    Co-Authors: Shuichi Hamada, Yasushi Shimada, Tadashi Imamura, Wakako Ohyama, Rie Takashima, Keisuke Shimada, Kazumi Matsumoto, Satoru Kawakami, Shoji Matsumura, Hisakazu Sanada
    Abstract:

    Abstract The repeated-dose liver micronucleus (RDLMN) assay using young adult rats has the potential to detect hepatocarcinogens. We conducted a collaborative study to assess the performance of this assay and to evaluate the possibility of integrating it into general toxicological studies. Twenty-four testing laboratories belonging to the Mammalian Mutagenicity Study Group, a subgroup of the Japanese Environmental Mutagen Society, participated in this trial. Twenty-two model chemicals, including some hepatocarcinogens, were tested in 14- and/or 28-day RDLMN assays. As a result, 14 out of the 16 hepatocarcinogens were positive, including 9 genotoxic hepatocarcinogens, which were reported negative in the bone marrow/peripheral blood micronucleus (MN) assay by a single treatment. These outcomes show the high sensitivity of the RDLMN assay to hepatocarcinogens. Regarding the specificity, 4 out of the 6 non-liver targeted genotoxic carcinogens gave negative responses. This shows the high organ specificity of the RDLMN assay. In addition to the RDLMN assay, we simultaneously conducted gastrointestinal tract MN assays using 6 of the above carcinogens as an optional trial of the collaborative study. The MN assay using the glandular stomach, which is the first contact site of the test chemical when administered by oral gavage, was able to detect chromosomal aberrations with 3 test chemicals including a stomach-targeted carcinogen. The treatment regime was the 14- and/or 28-day repeated-dose, and the regime is sufficiently promising to incorporate these methods into repeated-dose toxicological studies. The outcomes of our collaborative study indicated that the new techniques to detect chromosomal aberrations in vivo in several tissues worked successfully.

  • evaluation of a liver micronucleus assay in young rats iv a study using a double dosing single sampling method by the collaborative study group for the micronucleus test csgmt japanese Environmental Mutagen society jems mammalian Mutagenicity study g
    Mutation Research-genetic Toxicology and Environmental Mutagenesis, 2010
    Co-Authors: Hironao Takasawa, Hiroshi Suzuki, Izumi Ogawa, Yasushi Shimada, Kazuo Kobayashi, Yukari Terashima, Hirotaka Matsumoto, Keiyu Oshida, Ryo Ohta, Tadashi Imamura
    Abstract:

    A collaborative study was conducted to evaluate whether a liver micronucleus assay using four-week-old male F344 rats can be used to detect genotoxic rat hepatocarcinogens using double-dosing with a single-sampling 4 days after the second dose. The assay methods were thoroughly validated by the seven laboratories involved in the study. Seven chemicals, 2,4-diaminotoluene, diethyl nitrosamine, p-dimethylaminoazobenzene, 1,2-dimethylhydrazine dihydrochloride, 2,4-dinitrotolunene, 2,6-dinitrotoluene and mitomycin C, known to produce positive responses in the single-dosing/triple-sampling method were selected for use in the present study, and each chemical was examined in two laboratories with the exception of 2,4-dinitrotolunene. Although several of the compounds were examined at lower doses for reasons of toxicity than in the single-dosing/triple-sampling method, all chemicals tested in the present study induced micronuclei in liver cells indicating a positive result. These findings suggest that the liver micronucleus assay can be used in young rats to detect genotoxic rat hepatocarcinogens using a double-dosing/single-sampling procedure. Further, the number of animals used in the liver micronucleus assay can be reduced by one-third to a half by using the double-dosing/single-sampling method. This reduction in animal numbers also has significant savings in time and resource for liver perfusion and hepatocyte isolation.

  • evaluation of a liver micronucleus assay in young rats iii a study using nine hepatotoxicants by the collaborative study group for the micronucleus test csgmt japanese Environmental Mutagen society jems mammalian Mutagenicity study group mms
    Mutation Research-genetic Toxicology and Environmental Mutagenesis, 2010
    Co-Authors: Hironao Takasawa, Hiroshi Suzuki, Izumi Ogawa, Yasushi Shimada, Kazuo Kobayashi, Yukari Terashima, Hirotaka Matsumoto, Keiyu Oshida, Chinami Aruga, Ryo Ohta
    Abstract:

    Abstract We have been investigating a liver micronucleus assay to detect genotoxic chemicals using young rats for several years, and had established its advantages with respect to using autonomous proliferation of young rat hepatocytes. Nine chemicals known to induce hepatotoxic effects such as necrosis (2,6-dinitrotolune, bromobenzene, isoniazid, phenacetin, allyl alcohol and thioacetamide), cholestasis (chlorpromazine hydrochloride and α-naphthyl isothiocyanate) and oxidative stress (clofibrate) were selected for this study. A liver micronucleus assay was conducted in 4-week-old male F344 rats using two or three dose levels of test chemicals given orally by gavage to evaluate the compound's ability to induce micronucleated hepatocytes. Several of these test chemicals were additionally examined in a peripheral blood micronucleus assay conducted concurrently and in the same animals. The genotoxic rodent hepatocarcinogen, 2,6-dinitrotoluene showed a positive result in the liver micronucleus assay, but the nongenotoxic hepatocarcinogens, clofibrate and thioacetamide gave negative responses. Bromobenzene, known to produce DNA adducts but is noncarcinogenic in rodent liver, was judged equivocal in this assay. α-Naphthyl isothiocyanate is noncarcinogenic and showed negative response in the liver. The other four chemicals, known to be either noncarcinogenic or carcinogenic in other non-liver target organs, showed negative results in the liver micronucleus assay. Based on the results in the present study and previous report described above, it was concluded that this technique is able to effectively predict genotoxic rodent hepatocarcinogenicity, and does not give false positives due to hepatotoxicity.

  • evaluation of a liver micronucleus assay with 12 chemicals using young rats ii a study by the collaborative study group for the micronucleus test japanese Environmental Mutagen society mammalian Mutagenicity study group
    Mutagenesis, 2008
    Co-Authors: Hiroshi Suzuki, Hironao Takasawa, Izumi Ogawa, Yasushi Shimada, Kazuo Kobayashi, Yukari Terashima, Tadashi Imamura, Jin Tanaka, Atsushi Miyazaki, Makoto Hayashi
    Abstract:

    : The partial hepatectomy method, co-treatment method with mitogens and an in vivo/in vitro assay method have been reported as in vivo liver micronucleus (MN) assays. These methods have disadvantages with respect to widespread use as an in vivo assay, i.e. they are time consuming, labour intensive and there is the possibility of interaction with the mitogens used. Therefore, we have attempted to develop a new method to overcome these disadvantages. The assay as described herein utilises the autonomous proliferation of hepatocytes of young rats. Nine chemicals have been evaluated using this method thus far. We have also assessed the sensitivity and detectability according to the following methods. A liver MN assay was performed in two strains of young rats using one or two doses of 12 chemicals to investigate the inducibility of micronucleated hepatocytes. For some of the chemicals, a peripheral blood MN assay was performed concurrently in the same animals. The following chemicals were used: diethylnitrosamine (DEN), 2-acetylaminofluorene (2AAF), 2,4-diaminotoluene (2,4-DAT), quinoline, p-dimethylaminoazobenzene (DAB), dimethylnitrosamine (DMN), ethylmethanesulphonate, 5-fluorouracil, mitomycin C (MMC), 1,2-dimethylhydrazine.2HCl, cyclophosphamide and 2,4-dinitrotoluene (2,4-DNT). The rodent hepatocarcinogens, quinoline, DAB and DMN showed positive responses in previous assays. The results of the present assay revealed new positive responses for single doses of 2AAF, 2,4-DAT, MMC, 1,2-dimethylhydrazine.2HCl and 2,4-DNT. These chemicals are known rodent hepatocarcinogens, whose clastogenicity is believed to be related to the formation of reactive metabolites generated through enzymatic activation, or the chemicals act directly. Two doses of 2AAF and DMN appeared to be more effective than a single dose in terms of MN induction. Although there were quantitative differences in the incidences of MNs, both strains of rat (F344 and SD) responded positively after treatment with DEN, DMN, 2,4-DAT, DAB, quinoline and 2AAF, suggesting that both strains are appropriate for the assay. Based on these results, it is concluded that this technique could be effective for detecting chemical clastogenicity in hepatocytes in vivo.

  • evaluation of liver and peripheral blood micronucleus assays with 9 chemicals using young rats a study by the collaborative study group for the micronucleus test csgmt japanese Environmental Mutagen society jems mammalian Mutagenicity study group mms
    Mutation Research-genetic Toxicology and Environmental Mutagenesis, 2005
    Co-Authors: Hiroshi Suzuki, Yasushi Shimada, Kazuo Kobayashi, Yukari Terashima, Naohiro Ikeda, Takayoshi Suzuki, Toshiyuki Hagiwara, Shigeki Hatakeyama, Koko Nagaoka, Junichi Yoshida
    Abstract:

    Abstract We conducted simultaneous liver and peripheral blood micronucleus assays in young rats with seven rodent hepatocarcinogens—4,4′-methylenedianiline (MDA), quinoline, o -toluidine, 4-chloro- o -phenylenediamine (CPDA), dimethylnitrosamine (DMN), p -dimethylaminoazobenzene (DAB), and di(2-ethylhexyl)phthalate (DEHP)—and two Mutagenic chemicals—kojic acid and methylmethanesulfonate (MMS). Quinoline, DMN, and DAB were positive in the liver assay, while o -toluidine, kojic acid, DAB, and MMS were positive in the peripheral blood assay. o -Toluidine, kojic acid, and DAB are reportedly negative in mouse bone marrow micronucleus assays, indicating a species difference. Our results revealed a correlation between micronucleus induction in hepatocytes and hepatocarcinogenicity. This technique can be useful for the detection of micronucleus-inducing chemicals that require metabolic activation, and it enables simultaneous comparison of the micronucleus-inducing potential of chemicals in the liver and peripheral blood in the same individual.

D J Kirkland - One of the best experts on this subject based on the ideXlab platform.

  • Statistical evaluation of Mutagenicity test data: recommendations of the U.K. Environmental Mutagen Society.
    Environmental health perspectives, 1994
    Co-Authors: D J Kirkland
    Abstract:

    Most of the many published guidelines on how to conduct Mutagenicity tests do not give advice or references on statistical analysis of data. The U.K. Environmental Mutagen Society decided to address this omission, and in 1985 established 8 working groups comprising genetic toxicologists from all sectors of the science, plus at least 2 statisticians per group, to produce statistics guidelines on 10 different test systems. Each group gave advice on how to determine the suitability of data for distribution fitting, when data are unsuitable, when and how data should be transformed, which statistical tests are suitable for a given set of data, which factors govern the choice of statistical test, an order of preference, and some worked examples using real data. In addition, groups gave advice on statistical issues in the design of experiments. Strong recommendations were made that for in vitro tests, sufficient cells be treated and sampled to provide meaningful values of spontaneous mutant/aberration frequencies, for genuine, independent replicate treatments to be used, and that the acceptability of an experiment should be based on homogeneity between replicates as well as comparison of negative and positive control responses with historical ranges. It was recommended that most in vitro studies should include independent repeat experiments, and advice was given on how to check for consistency between experiments and then combine data for further significance testing.(ABSTRACT TRUNCATED AT 250 WORDS)

  • Statistical Evaluation of Mutagenicity Test Data: Recommendations of the U.K. Environmental Mutagen Society
    Environmental Health Perspectives, 1994
    Co-Authors: D J Kirkland
    Abstract:

    analysis of data. The U.K. Environmental Mutagen Society decided to address this omission, and in 1985 established 8 working groups comprising genetic toxicologists from all sectors of the science, plus at least 2 statisticians per group, to produce statistics guidelines on 10 different test systems. Each group gave advice on how to determine the suitability of data for distribution fitting, when data are unsuitable, when and how data should be transformed, which statistical tests are suitable for a given set of data, which factors govern the choice of statistical test, an order of preference, and some worked examples using real data. In addition, groups gave advice on statistical issues in the design of experiments. Strong recommendations were made that for in vitro tests, sufficient cells be treated and sampled to provide meaningful values of spontaneous mutant/aberration frequencies, for genuine, independent replicate treatments to be used, and that the acceptability of an experiment should be based on homogeneity between replicates as well as comparison of negative and positive control responses with historical ranges. It was recommended that most in vitro studies should include independent repeat experiments, and advice was given on how to check for consistency between experiments and then combine data for further significance testing. For in vivo tests, it was generally believed that increasing the number of dose levels and reducing the number of animals per dose impoves statistical sensitivity; there was some uncertainty about how to handle data when heterogeneity was found within a group of animals, but there was a consensus that statistical tests and interpretation of the biological findings should proceed.

Shigeharu Muto - One of the best experts on this subject based on the ideXlab platform.

  • Standard protocol for the total red blood cell Pig-a assay used in the interlaboratory trial organized by the Mammalian Mutagenicity Study Group of the Japanese Environmental Mutagen Society
    Genes and Environment, 2019
    Co-Authors: Satsuki Chikura, Shigeharu Muto, Takafumi Kimoto, Satoru Itoh, Hisakazu Sanada, Katsuyoshi Horibata
    Abstract:

    The Pig-a assay, a promising tool for evaluating in vivo genotoxicity, is based on flow cytometric enumeration of red blood cells (RBCs) that are deficient in glycosylphosphatidylinositol anchor protein. Various approaches for measuring Pig-a mutant cells have been developed, particularly focusing on measuring mutants in peripheral RBCs and reticulocytes (RETs). The Pig-a assay on concentrated RETs—the PIGRET assay—has the potential to detect genotoxicity in the early stages of a study. To verify the potential and usefulness of the PIGRET assay for short-term testing, we conducted an interlaboratory trial involving 16 laboratories organized by the Mammalian Mutagenicity Study Group of the Japanese Environmental Mutagen Society (MMS/JEMS). The collaborating laboratories assessed the Mutagenicity of a total of 24 chemicals in rats using a single-treatment design and standard protocols for conducting the Pig-a assay on total RBCs (the RBC Pig-a assay) and the PIGRET assay. Here, we describe the standard protocol for the RBC Pig-a assay in detail.

  • challenges of young scientists at the cutting edge of genotoxicity research the open symposium of the japanese Environmental Mutagen society jems 2018
    Genes and Environment, 2018
    Co-Authors: Manabu Yasui, Shigeharu Muto, Akira Sassa
    Abstract:

    The Open Symposium of the Japanese Environmental Mutagen Society (JEMS) entitled “Challenges of Young Scientists at the Cutting-edge of Genotoxicity Research” was held in the Main Conference Room of the Foundation for Promotion of Cancer Research, Tokyo, on June 9th, 2018. This year, the symposium aimed to provide an opportunity to highlight the cutting-edge research activities of young scientists who are continuing to expand frontiers of the fields of Environmental Mutagenesis and genetic toxicology; it also aimed to inform JEMS activities to the participants. Through this report, the organizers present a summary of the symposium.

  • evaluation of the Mutagenicity of alkylating agents methylnitrosourea and temozolomide using the rat pig a assay with total red blood cells or reticulocytes
    Mutation Research-genetic Toxicology and Environmental Mutagenesis, 2016
    Co-Authors: Shigeharu Muto, Katsuya Yamada, Tatsuya Kato, Masamitsu Ando, Yoshimi Inoue, Yumiko Iwase, Yoshifumi Uno
    Abstract:

    Abstract A collaborative study of the endogenous phosphatidylinositol glycan class A ( Pig-a ) gene mutation assay was conducted by the Japanese Environmental Mutagen Society/Mammalian Mutagenicity Study Group with a single-dosing regimen of test chemicals administered to male rats. As a part of the study, two DNA alkylating agents, methylnitrosourea (MNU) and temozolomide (TMZ), were dosed by single oral gavage at 25, 50, and 100 mg/kg body weight. Pig-a mutant analysis of total red blood cells (RBCs; RBC Pig-a assay) and reticulocytes (RETs; PIGRET assay) was performed on Days 8, 15 and 29 after the administration. Both chemicals increased Pig-a mutants among RBCs and RETs with dose dependency on all days examined. The mutant frequencies were higher among RETs compared with RBCs, indicating that the PIGRET assay could detect Mutagenicity more sensitively than the RBC Pig-a assay after a single dose of test chemicals.