title: Chronic alcohol exposure induces genome damage measured using the cytokinesis-block micronucleus cytome assay and aneuploidy in human B lymphoblastoid cell lines.
abstract: Excessive alcohol consumption is associated with an increased risk of a variety of cancers. The specific association between alcohol consumption and increased risk of breast cancer has been a consistent finding in numerous studies to date; however, the biological mechanism remains unknown. One possibility is that alcohol induces chromosome instability and aneuploidy events commonly seen in cancer. The cytokinesis-block micronucleus cytome assay was used to assess the ability of alcohol to induce DNA damage and aneuploidy in two human B lymphoblastoid cell lines--WIL2-NS and GM13705. The cells were treated chronically with physiologically relevant levels of alcohol (0.36 and 1.35% v/v) for a period of 6 weeks. Results demonstrate that in these cell lines, chronic treatment with alcohol induces micronuclei, nucleoplasmic bridges and nuclear buds, indicative of the various genome damaging events of chromosome loss and breakage, asymmetric chromosome rearrangement and gene amplification, respectively. Using chromogenic in situ hybridisation, we measured chromosome 17 aneuploidy in these cell lines. Results from this assay indicate that chronic treatment of alcohol induces aneuploidy (measured as chromosome 17 aneuploidy) in both cell lines. The results from this study support the hypothesis that alcohol is a probable cause of cancer initiation by inducing chromosomal instability and aneuploidy, which may be a result of multiple indirect mechanisms.
authors.affiliation: Commonwealth Scientific and Industrial Research Organisation Food and Nutritional Sciences, Nutritional Genomics & Genome Health Diagnostics, Gate 13 Kintore Ave, Adelaide, South Australia 5000, Australia. bianca.benassi@csiro.au
authors.forename: Bianca
authors.initials: B
authors.lastname: Benassi-Evans
authors.forename: Michael
authors.initials: M
authors.lastname: Fenech
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects*; D000704:Analysis of Variance; D000782:Aneuploidy; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D002460:Cell Line; D002886:Chromosomes, Human, Pair 17 / Q000187:drug effects* / Q000235:genetics; D048749:Cytokinesis / Q000187:drug effects; D004249:DNA Damage / Q000235:genetics*; D000431:Ethanol / Q000633:toxicity*; D006801:Humans; D017403:In Situ Hybridization; D016014:Linear Models; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*
chemical_list: D000431:Ethanol