Comparison of L5178Y tk^(+/-) Mouse Lymphoma Assay and In vitro Chromosome Aberration Test

Michael Lee; Jung Kwon; Ji-Hee Cho; Mi-Young Hong; Eun-Joo Kim

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자료유형: 학술저널

저자정보: Michael Lee Jung Kwon Ji-Hee Cho Mi-Young Hong Eun-Joo Kim

저널정보: 한국독성학회 Toxicological Research Journal of Toxicology and Public Health Vol.18 No.2

발행연도: 2002.6

수록면: 129 - 138 (10page)

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The mouse lymphoma assay (MLA) has been recently validated as a sensitive and specific test system to determine the genotoxic potential for a chemical. The objective of this study is to evaluate the utility of MLA for detecting mutagens. Especially, to compare MLA with the in vitro chromosomal aberration test (CA), we performed MLA using the microwell method with three chemicals (hydroxyurea, theophylline and amino acid copper complex), which were reportedly positive in the CA. In cells treated with hydroxyurea, anti-neoplastic agent that blocks DNA replication, evidence of a positive response was obtained without S9 mix for 4 h and 24 h. In addition, analysis of colony size distribution at concentration that gave an elevated mutant fraction showed that hydroxyurea induced a high proportion of small type colonies, indicating that hydroxyurea-induced mutation is associated with large chromosomal deletions. Conversely, negative MLA result was obtained for theophylline, which was used as central nervous system stimulator. Although theophylline increased the mutant frequency at concentration of 1250 ㎍/ml with S9 mix for 4 h, a concentration-related increase in mutant frequency was not observed. The MLA result of amino acid copper complex was considered equivocal because the positive result was obtained at concentrations showing 10% or less RS or RTG. Thus, among 3 CA-positive chemicals, positive MLA result was obtained for one. The other two chemicals were negative and equivocal. However. MLA, which evaluates mutagenic potential of chemicals through colony formation by cell growth, may provide a higher predictivity of carcinogenesis than CA.

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