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
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
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.