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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 Study Group (MMS)

Hamada, Shuichi ; Sutou, Sizuyo ; Morita, Takeshi ; Wakata, Akihiro ; Asanami, Shougo ; Hosoya, Satoko ; Ozawa, Shigenari ; Kondo, Koji ; Nakajima, Madoka ; Shimada, Hiroyasu ; Osawa, Koichi ; Kondo, Yasushi ; Asano, Norihide ; Sato, Sei-ichi ; Tamura, Hironobu ; Yajima, Nobuhiro ; Marshall, Richard ; Moore, Catherine ; Blakey, David H. ; Schechtman, Leonard M. ; Weaver, James L. ; Torous, Dorothea K. ; Proudlock, Ray ; Ito, Seiichi ; Namiki, Chiaki ; Hayashi, Makoto

Environmental and molecular mutagenesis, 2001, Vol.37 (2), p.93-110 [Periódico revisado por pares]

New York: John Wiley & Sons, Inc

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  • Título:
    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 Study Group (MMS)
  • Autor: Hamada, Shuichi ; Sutou, Sizuyo ; Morita, Takeshi ; Wakata, Akihiro ; Asanami, Shougo ; Hosoya, Satoko ; Ozawa, Shigenari ; Kondo, Koji ; Nakajima, Madoka ; Shimada, Hiroyasu ; Osawa, Koichi ; Kondo, Yasushi ; Asano, Norihide ; Sato, Sei-ichi ; Tamura, Hironobu ; Yajima, Nobuhiro ; Marshall, Richard ; Moore, Catherine ; Blakey, David H. ; Schechtman, Leonard M. ; Weaver, James L. ; Torous, Dorothea K. ; Proudlock, Ray ; Ito, Seiichi ; Namiki, Chiaki ; Hayashi, Makoto
  • Assuntos: 28-day treatment ; Animals ; Biological and medical sciences ; CSGMT ; Intensive care medicine. Antipoison centers ; Japan ; Male ; Medical sciences ; micronucleus assay ; Micronucleus Tests - standards ; mitomycin C ; mouse ; Mutagens - toxicity ; rat ; Rats ; Toxicology
  • É parte de: Environmental and molecular mutagenesis, 2001, Vol.37 (2), p.93-110
  • Notas: ark:/67375/WNG-LLT9BBHX-4
    Tsutikawa Memorial Fund for Study in Mammalian Mutagenicity
    ArticleID:EM1017
    istex:547E1E3AA4EC9EB461AAC254F6FBC4D97374487D
    ObjectType-Article-2
    SourceType-Scholarly Journals-1
    ObjectType-Feature-1
    content type line 23
  • Descrição: 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. Environ. Mol. Mutagen. 37:93–110, 2001 © 2001 Wiley‐Liss, Inc.
  • Editor: New York: John Wiley & Sons, Inc
  • Idioma: Inglês
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