title: Influence of donor age on vinblastine-induced chromosome malsegregation in cultured peripheral lymphocytes.
abstract: The incidence of spontaneous aneuploidy in human somatic and germ cells is known to be positively associated with aging. However, the influence of age on the individual susceptibility to chemically induced chromosome malsegregation has not been elucidated. In this study the spindle poison vinblastine (VBL) was used as a model compound to assess the influence of donor age on chemically induced chromosome malsegregation in cultured lymphocytes. Blood cultures from 20 female donors belonging to two different age groups (10 <30 years and 10 >50 years) were treated with VBL (7.5 ng/ml) from 43 h after mitogen stimulation until harvest at 60 h, i.e. during the time interval corresponding to G2/M. In order to block cytokinesis, cytochalasin B (6 microg/ml) was added to cultures at 44 h. For each donor the incidence of micronuclei, polyploidy and malsegregation (non-disjunction and loss) of chromosomes X and 8 was determined using fluorescence in situ hybridization with chromosome-specific centromeric probes. Both background incidence of micronuclei and spontaneous chromosome X non-disjunction were significantly elevated in older donors. Individual responses to VBL treatment showed wide interindividual variability, which was not significantly associated with the age of the donor. In both age classes chromosome X was more susceptible than chromosome 8 to both spontaneous and VBL-induced malsegregation. These results indicate that donor age has a limited influence on the aneugenic effects exerted by VBL in peripheral lymphocytes in vitro. Other factors have to be considered to account for the large interindividual variation in sensitivity to VBL challenge observed in this work.
authors.affiliation: Laboratory of Comparative Toxicology and Ecotoxicology,Istituto Superiore Sanità, Viale Regina Elena 299, I-00161 Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Leopardi
authors.forename: Francesca
authors.initials: F
authors.lastname: Marcon
authors.forename: Gabriella
authors.initials: G
authors.lastname: Dobrowolny
authors.forename: Andrea
authors.initials: A
authors.lastname: Zijno
authors.forename: Riccardo
authors.initials: R
authors.lastname: Crebelli
mesh_terms: D000328:Adult; D000375:Aging / Q000097:blood / Q000235:genetics* / Q000473:pathology; D000782:Aneuploidy; D002478:Cells, Cultured / Q000187:drug effects / Q000648:ultrastructure; D020090:Chromosome Segregation / Q000187:drug effects*; D002877:Chromosomes, Human / Q000187:drug effects*; D002898:Chromosomes, Human, Pair 8 / Q000187:drug effects; D003571:Cytochalasin B / Q000494:pharmacology; D004351:Drug Resistance; D005260:Female; D014644:Genetic Variation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008214:Lymphocytes / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D015162:Micronucleus Tests; D008875:Middle Aged; D009630:Nondisjunction, Genetic; D008941:Spindle Apparatus / Q000187:drug effects*; D014747:Vinblastine / Q000494:pharmacology* / Q000633:toxicity; D014960:X Chromosome / Q000187:drug effects
chemical_list: D003571:Cytochalasin B; D014747:Vinblastine