PMID- 10474821 OWN - NLM STAT- MEDLINE DCOM- 19991008 LR - 20190513 IS - 0267-8357 (Print) IS - 0267-8357 (Linking) VI - 14 IP - 1 DP - 1999 Jan TI - Noscapine hydrochloride disrupts the mitotic spindle in mammalian cells and induces aneuploidy as well as polyploidy in cultured human lymphocytes. PG - 51-6 AB - Noscapine hydrochloride is a centrally acting antitussive opium derivative widely used in cough suppressants. Recent studies have reported that noscapine is a potent inducer of polyploidy but not of aneuploidy in vitro. To obtain more comprehensive information about the cytogenetic effects of this compound, we treated cultured human lymphocytes (HPL) and Chinese hamster ovary (CHO) cells with various concentrations of noscapine hydrochloride. Using a differential staining technique noscapine was shown to disrupt the mitotic spindle at concentrations < 5 micrograms/ml in both cell types. The use of multicolor fluorescence in situ hybridization (FISH) on noscapine-treated human lymphocytes showed a dose-dependent induction of hyperdiploidy of chromosome 1 but not of chromosomal breakage in the 1cen-q12 region under in vitro conditions, indicating that noscapine is specifically inducing numerical chromosomal aberrations. FISH with probes targeting different chromosomes revealed that noscapine is capable of inducing both polyploidy and true hyperdiploidy. Our results show that noscapine, by disrupting the function of the mitotic spindle, has the ability to induce aneuploidy and not uniquely polyploidy as previously reported. By using these types of molecular cytogenetic techniques, it should be possible to evaluate the ability of noscapine to induce aneuploidy in the upper intestinal tract in vivo. FAU - Schuler, M AU - Schuler M AD - Environmental Toxicology Graduate Program, University of California, Riverside 92521, USA. FAU - Muehlbauer, P AU - Muehlbauer P FAU - Guzzie, P AU - Guzzie P FAU - Eastmond, D A AU - Eastmond DA LA - eng PT - Journal Article PL - England TA - Mutagenesis JT - Mutagenesis JID - 8707812 RN - 8V32U4AOQU (Noscapine) SB - IM MH - *Aneuploidy MH - Animals MH - CHO Cells MH - Cells, Cultured MH - Cricetinae MH - Dose-Response Relationship, Drug MH - Humans MH - In Situ Hybridization, Fluorescence/methods MH - Lymphocytes/*drug effects MH - Mutagenesis MH - Noscapine/*toxicity MH - *Polyploidy MH - Spindle Apparatus/*drug effects EDAT- 1999/09/04 00:00 MHDA- 1999/09/04 00:01 CRDT- 1999/09/04 00:00 PHST- 1999/09/04 00:00 [pubmed] PHST- 1999/09/04 00:01 [medline] PHST- 1999/09/04 00:00 [entrez] AID - 10.1093/mutage/14.1.51 [doi] PST - ppublish SO - Mutagenesis. 1999 Jan;14(1):51-6. doi: 10.1093/mutage/14.1.51.