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.
Migliore
L
L
Dipartimento di Scienze dell'Ambiente e del Territorio, Università di Pisa, Via S Giuseppe 22, 56100 Pisa, Italy.
Cocchi
L
L
Scarpato
R
R
D000079:Acetaldehyde / Q000633:toxicity; D000782:Aneuploidy; D002503:Centromere / Q000235:genetics*; D004054:Diethylstilbestrol / Q000031:analogs & derivatives / Q000633:toxicity; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006118:Griseofulvin / Q000633:toxicity; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000648:ultrastructure*; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*
D009153:Mutagens; D006118:Griseofulvin; D004054:Diethylstilbestrol; D000079:Acetaldehyde; C000937:diethylstilbestrol dipropionate