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논문KCI 등재

설치류 생식세포에서의 우성치사 돌연변이 분석의 평가

Evaluation of Dominant-Lethal Mutation Assays in Rodent Germ Cells

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초록

The basic principle of the dominance lethality test was to expose a male animal to a test substance and then mate with a female that was not exposed to the test substance. In this test, male and female ICR mice were used and three positive substances (Cyclophosphamide, Ethyl methanesulphonate, and Chlorambucil) specified in the guideline were used. Sodium chloride, known to be non-toxic, was used as a comparative material. The test method and observation items were mated weekly with females not exposed to the test substance after single and repeated administration to male mice. Then, during the observation period, systemic symptoms, body weight, and food intake were measured. After the observation period, organ weights, autopsy, and caesarean section were performed to calculate embryo loss rates, fetal mortality rates, and dominant mortality rates before and after implantation. As a result, a dose-dependently dominant mortality rate was observed in the male positive test substance group, which was judged to be a change caused by the test substance. The results of this test were consistent with the guidelines. Therefore, the test substances Cyclophosphamide, Ethyl methanesulphonate, and Chlorambucil were judged to be substances capable of inducing dominant lethal mutations.

Abstract

The basic principle of the dominance lethality test was to expose a male animal to a test substance and then mate with a female that was not exposed to the test substance. In this test, male and female ICR mice were used and three positive substances (Cyclophosphamide, Ethyl methanesulphonate, and Chlorambucil) specified in the guideline were used. Sodium chloride, known to be non-toxic, was used as a comparative material. The test method and observation items were mated weekly with females not exposed to the test substance after single and repeated administration to male mice. Then, during the observation period, systemic symptoms, body weight, and food intake were measured. After the observation period, organ weights, autopsy, and caesarean section were performed to calculate embryo loss rates, fetal mortality rates, and dominant mortality rates before and after implantation. As a result, a dose-dependently dominant mortality rate was observed in the male positive test substance group, which was judged to be a change caused by the test substance. The results of this test were consistent with the guidelines. Therefore, the test substances Cyclophosphamide, Ethyl methanesulphonate, and Chlorambucil were judged to be substances capable of inducing dominant lethal mutations.

참고문헌 (12)

  1. "OECD Guidelines for The Testing of Chemicals, 478, Rodent Dominant Lethal Test Organisation for Economic Co-operation and Development", ~ (2016)
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  4. Gebhardt, D.O.E., "The embryolethal and teratogenic effects of cyclophosphamide on mouse embryos", Cancer Res, 3, pp.273~278 (1970)
  5. Loveless, A., "Increased rate of plaque-type and host-range mutation following treatment of bacteriophage in vitro with ethyl methanesulphonate", Nature (London), 181, pp.1212~1213 (1958)
  6. Gary A. Sega, "A review of the genetic effects of ethyl methanesulfonate", Mutation Research, 134, pp.113~142 (1984)
  7. IARC Supplement 7, "Overall Evaluations of Carcinogenicity:An Updating of IRAC Monographs, vols. 1-42", International Agency for Research on Cancer, ~ (1987)
  8. IARC, "Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans: Some Antineoplastic and Immunosuppressive Agents, vol. 26", International Agency for Research on Cancer, ~ (1981)
  9. R. L. Dedrick, "Carcinogenic potency of alkylating agents in rodents and humans", Cancer Res, 52, pp.2464~2467 (1992)
  10. SRI International, An evaluation of the mutagenic potential of chlornaphazine utilizing the in vitro cytogenetics assay in Chinese hamster ovary cells, "B. E. Stewart", Government Printing Office, ~, pp.EPA-68-02-3702; SRI Project LSU-3447 (1983)
  11. M. H. Greene, "Acute nonlymphocytic leukemia after therapy with alkylating agents for ovarian cancer. A study of five randomized clinical trials", N. Engl. J. Med, 307, pp.1416~1421 (1982)
  12. K. L. Witt, "Mouse bone marrow micronucleus test results do not predict the germ cell mutagenicity of N-hydroxymethylacrylamide in the mouse dominant lethal assay, Eviron", Mol. Mutagen, 41, pp.111~120 (2003)

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