title: Origin of aneuploidy in relation to disturbances of cell-cycle progression. I. Effects of vinblastine on mouse bone marrow cells.
abstract: Vinblastine (VBL) was tested in the mouse for induction of chromosome malsegregation in bone marrow cells. The occurrence of aneuploidy and polyploidy was correlated with cell-cycle kinetics measured by DNA labelling with bromodeoxyuridine (BrdUrd). Sister-chromatid exchanges (SCE) were also detected. A dose-dependent lengthening of the cell cycle was induced in the dose range of 0.9-4.5 mg/kg body weight, up to a complete inhibition of cell-cycle progression (100% of metaphases were arrested before completion of the first mitotic division following a recovery time of 18 h, compared with 8% in the controls). Both aneuploidy and polyploidy were induced. Aneuploid metaphases were grouped into 2 classes, those with no more than 2 extra chromosomes and those with 3-10 extra chromosomes. The frequencies of cells with severe aneuploidy and polyploidy increased considerably when second-generation cells were sampled at a recovery time of 24 h. This observation suggested that gross chromosome imbalances occur preferentially after a period of mitotic arrest, probably as a consequence of multipolar spindles or failure of proper spindle assembly. Non-disjunction of single chromosomes arises independently of the mitotic block. A slight increase in SCE frequency was observed only at a recovery time of 18 h. This study may provide information on the kinetics and mechanisms of origin of VBL-induced numerical aberrations in vivo.
authors.affiliation: ENEA, C.R.E. Casaccia, Laboratory of Toxicology, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Manca
authors.forename: B
authors.initials: B
authors.lastname: Bassani
authors.forename: A
authors.initials: A
authors.lastname: Russo
authors.forename: F
authors.initials: F
authors.lastname: Pacchierotti
mesh_terms: D000704:Analysis of Variance; D000782:Aneuploidy; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000648:ultrastructure*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002875:Chromosomes / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D008297:Male; D051379:Mice; D012044:Regression Analysis; D014747:Vinblastine / Q000494:pharmacology*
chemical_list: D014747:Vinblastine