Evaluation of micronuclei and chromosomal breakage in the 1cen-q12 region by the butadiene metabolites epoxybutene and diepoxybutane in cultured human lymphocytes.
1,3-Butadiene is a widely used industrial chemical and common environmental pollutant that has been associated with increased risks of leukemias and lymphomas. Butadiene and its metabolites, 1, 2-epoxybutene (EB) and diepoxybutane (DEB), have been shown to be genotoxic in a wide variety of test organisms. The objective of this research was to evaluate techniques for the rapid detection of chromosomal alterations occurring in humans exposed to butadiene. We have used a multicolored fluorescence in situ hybridization (FISH) method and the CREST-modified micronucleus assay to detect chromosomal breakage induced by EB (10-300 microM) and DEB (0.5-10 microM) in cultured human lymphocytes. A significant dose-related increase in the formation of micronuclei was seen in lymphocytes treated with DEB at concentrations as low as 2.5 microM, but not with EB over the dose range tested. Over 80% of the micronuclei induced by DEB were CREST-negative, indicating their origin from chromosomal breakage. Multicolor FISH using two adjacent chromosome-specific probes showed a significant increase in chromosomal breakage in the 1cen-q12 region induced by DEB at concentrations as low as 2.5 microM, but not by EB. Since DEB is likely to be one of the metabolites contributing to the genotoxic effects of butadiene, the sensitivity of the tandem FISH approach to detect breakage induced by diepoxybutane indicates that this technique may be useful for monitoring chromosomal alterations in butadiene-exposed workers.
Murg
M n
Mn
Environmental Toxicology Graduate Program, University of California, Riverside, CA 92521, USA.
Schuler
M
M
Eastmond
D A
DA
D002070:Butadienes / Q000378:metabolism*; D002273:Carcinogens / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D002503:Centromere / Q000187:drug effects; D019457:Chromosome Breakage; D002878:Chromosomes, Human, Pair 1; D002899:Chromosomes, Human, Pair 9; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000633:toxicity*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D018386:Kinetochores / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D016133:Polymerase Chain Reaction / Q000379:methods
D002070:Butadienes; D002273:Carcinogens; D004852:Epoxy Compounds; D009153:Mutagens; C024370:3,4-epoxy-1-butene; C007366:diepoxybutane