Detection of the centromere in micronuclei by fluorescence in situ hybridization: its application to the human lymphocyte micronucleus assay after treatment with four suspected aneugens.

The human lymphocyte micronucleus (MN) test combined with fluorescence in situ hybridization (FISH) of a centromeric probe is considered a useful screening assay to distinguish between clastogenic and aneugenic agents. Four suspected aneuploidy-inducing chemicals, acetaldehyde (AA), diethylstilbestrol (DES), diethylstilbestrol dipropionate (DESdp) and griseofulvin (GF), have been evaluated with the assay. All compounds induced a significant increase of MN at all doses tested. After the application of the FISH technique with a pancentromeric DNA sequence, DES, DESdp and GF showed a statistically significant increase in the percentage of positive signals compared with the control culture. GF induced the highest percentage of centromere-positive MN observed to date (>90% on average). AA did not show a significant difference in the percentage of centromere-positive MN. The results indicate that in human lymphocytes DES, DESdp and GF act primarily as aneugens, while AA seems capable of causing both chromosome breakage and aneuploidy.