EVALUATION OF THE IN-VITRO MICRONUCLEUS TEST AS AN ALTERNATIVE TO THEIN-VITRO CHROMOSOMAL ABERRATION ASSAY - POSITION OF THE GUM WORKING GROUP ON THE IN-VITRO MICRONUCLEUS TEST

Citation
B. Miller et al., EVALUATION OF THE IN-VITRO MICRONUCLEUS TEST AS AN ALTERNATIVE TO THEIN-VITRO CHROMOSOMAL ABERRATION ASSAY - POSITION OF THE GUM WORKING GROUP ON THE IN-VITRO MICRONUCLEUS TEST, Mutation research-reviews in mutation research, 410(1), 1998, pp. 81-116
Citations number
72
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Genetics & Heredity",Toxicology,"Biothechnology & Applied Migrobiology
Volume
410
Issue
1
Year of publication
1998
Pages
81 - 116
Database
ISI
SICI code
Abstract
In order to license a pharmaceutical or chemical, a compound has to be tested for several genotoxicity endpoints, including the induction of chromosomal aberrations in vitro. A working group within the GUM has evaluated published data on the in vitro micronucleus test with the ai m of judging its suitability as a replacement for the in vitro chromos omal aberration test. After strict rejection criteria were applied, a database including 96 publications and 34 compounds was obtained. For 30 of these compounds, data on both tests were available. For 24 of th e 30, concordant results in both test systems were obtained (80% corre lation). The discordant results in 6 compounds can be explained by a k nown or suspected aneugenic potential of these compounds. Considering that cell types and test protocols were extremely heterogeneous, this correlation is rather encouraging. Comparison of the different protoco ls, and experience established within the working group yielded severa l recommendations for the routine use of the in vitro micronucleus tes t. Although many cell lines are suitable, those most often used in gen otoxicity testing (e.g. CHL, CHO, V79, human lymphocytes, L5178Y mouse lymphoma cells) are recommended. Cytochalasin B may be used in the ca se of human lymphocytes; however, the possibility of its interaction w ith aneugenic test compounds should be considered. For continuously di viding cell lines, cytochalasin B is not recommended by the working gr oup. Although, there seems to be flexibility in the choice of treatmen t and sampling times, the average generation time of the chosen cell l ine of choice should be taken into account when determining sampling t ime, and treatment of cells for at least one cell cycle duration is re commended. The use of appropriate cytotoxicity tests is strongly recom mended. Although studies on some parameters of the test protocol may b e useful, the introduction of the in vitro micronucleus test into geno toxicity testing and guidelines should not be delayed. Even in its pre sent state, the in vitro micronucleus is a reliable genotoxicity test. Compared with the chromosomal aberration test, it detects aneugens mo re reliably, it is faster and easier to perform, and it has more stati stical pou er and the possibility of automation. (C) 1998 Elsevier Sci ence B.V.