INDUCTION OF CHROMOSOME-SPECIFIC ANEUPLOIDY AND MICRONUCLEI IN HUMAN-LYMPHOCYTES BY METABOLITES OF 1,3-BUTADIENE

1,3-Butadiene is a carcinogen in rodents, but its potential carcinogen icity to humans remains controversial, Numerous studies have shown tha t butadiene and its metabolites cause sister chromatid exchanges in vi tro and irt vivo. To test for other types of genotoxicity, the micronu cleus assay and fluorescence in situ hybridization (FISH) have been us ed to detect chromosome damage in human lymphocytes caused by two reac tive metabolites of butadiene, diepoxybutane (DEB) and monoepoxybutene (MEB), DEB (0.5-5.0 mu M) significantly increased micronucleus format ion 4- to 6-fold (P <0.01) and MEB (1-500 mu M) by 2- to 4-fold (P <0. 01) over control levels, The ability of DEB and MEB to induce aneuploi dy of chromosomes 7, 8, 12, and X was examined using dual-color FISH i n both interphase and metaphase cells, These chromosomes were chosen b ecause of their involvement in leukemogenesis, Both DEB and MEB caused dose-dependent increases in hyperdiploidy of chromosomes 12 and X, bu t had no discernible effect on chromosomes 7 and 8, These results sugg est that DEB and MEB cause chromosome-specific aneuploidy in human cel ls, If formed in sufficient amounts, DEB and MEB may produce chromosom e damage of the type found in leukemia following exposure to butadiene .