title: 1,2:3,4-Diepoxybutane Induces Multipolar Mitosis in Cultured Human Lymphocytes.
abstract: 1,3-Butadiene, a colorless gas regularly used in the production of plastics, thermoplastic resins, and styrene-butadiene rubber, poses an increased leukemia mortality risk to workers in this field. 1,3-Butadiene is also produced by incomplete combustion of motor fuels or by tobacco smoking. It is absorbed principally through the respiratory system and metabolized by several enzymes rendering 1,2:3,4-diepoxybutane (DEB), which has the highest genotoxic potency of all metabolites of 1,3-butadiene. DEB is considered a carcinogen mainly due to its high potential as clastogen, which induces structural chromosome aberrations such as sister chromatid exchanges, chromosomal breaks, and micronuclei. Due to its clastogenic effect, DEB is one of the most used agents for diagnostic studies of Fanconi anemia, a recessively inherited disease related to mutations affecting several genes involved in a common DNA repair pathway. When performing Fanconi anemia diagnostic tests in our laboratory, we have observed occasional multipolar mitosis (MM) in lymphocyte cultures exposed to 0.1 μg/ml of DEB and harvested in the absence of any mitotic spindle inhibitor. Although previous studies reported an aneugenic effect (i.e. it induces aneuploidy) of DEB, no mechanism was suggested to explain such observations. Therefore, the aim of this study was to investigate whether exposure to 0.1 μg/ml of DEB is significantly associated with the occurrence of MM. We blindly assessed the frequency of MM in lymphocyte cultures from 10 nonsmoking healthy individuals. Two series of 3 cultures were performed from each sample under different conditions: A, without DEB; B, with 0.1 μg/ml of DEB, and C, with 25 μM of mitomycin C as positive control. Cultures exposed to DEB showed higher frequencies of MM (23 of 2,000 cells) than did the unexposed ones (3 of 2,000 cells).
authors.affiliation: Divisix00F3;n de Genx00E9;tica, Centro de Investigacix00F3;n Biomx00E9;dica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Mx00E9;xico.
authors.forename: Reyna Lucía
authors.initials: RL
authors.lastname: Barajas Torres
authors.forename: Martín Daniel
authors.initials: MD
authors.lastname: Domínguez Cruz
authors.forename: César
authors.initials: C
authors.lastname: Borjas Gutiérrez
authors.forename: María de Lourdes
authors.initials: Mde L
authors.lastname: Ramírez Dueñas
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Magaña Torres
authors.forename: Juan Ramón
authors.initials: JR
authors.lastname: González García
mesh_terms: D000782:Aneuploidy; D002070:Butadienes / Q000378:metabolism / Q000633:toxicity; D002478:Cells, Cultured; D004852:Epoxy Compounds / Q000378:metabolism / Q000633:toxicity*; D064368:Healthy Volunteers; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000473:pathology; D016685:Mitomycin / Q000633:toxicity; D008938:Mitosis / Q000187:drug effects*; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity; D018675:Toxicity Tests
chemical_list: D002070:Butadienes; D004852:Epoxy Compounds; D009153:Mutagens; D016685:Mitomycin; C007366:diepoxybutane; C031763:1,3-butadiene