Susceptibility to induction of chromosomal damage by metabolites of 1,3-butadiene and its relationship to 'spontaneous' sister chromatid exchange frequencies in human lymphocytes.
Wiencke JK; Kelsey KT
Butadiene and styrene: assessment of health hazards. Sorsa M; Peltonen K; Vainio H; Hemminki K, eds. IARC scientific publications, No. 127, Lyon, France: International Agency for Research on Cancer, 1993 Dec; :265-273
An in-vitro method for the examination of potential individual variations in the induction of chromosomal damage by diepoxybutane (298180) in cultured peripheral blood lymphocytes was developed. A group of 173 healthy workers from four work populations was studied over a 3 year period. Blood samples were obtained from the subjects. Demographic data, age, occupation, medical history, and prior/present exposure to agents which could affect the sister chromatid exchange (SCE) assay were assessed via questionnaire. Work history and exposure to possible genotoxicants at the workplace from industrial hygiene sampling results were obtained. Cell cultures from blood lymphocytes were established and treated with 6 micromolar diepoxybutane, monoepoxybutene (930223), or nitrogen- mustard. After 24 hours, the cultures were treated with bromodeoxyuridine, processed, and stained differentially for the analysis of SCEs and chromosomal aberrations. A bimodal distribution of SCEs was observed. Approximately 20% of the subjects were twice as sensitive to SCE induction as the remaining population. Lymphocytes from sensitive individuals had nearly four times more chromatid deletions, 6.2 times more isochromatid deletions, and 19 times more chromatid exchanges induced by diepoxybutane. Diepoxybutane sensitive individuals were also observed to have higher frequencies of uninduced SCEs. Lymphocytes sensitive to diepoxybutane induced SCEs were shown to have a normal sensitivity to nitrogen-mustard and a significantly increased sensitivity to monoepoxybutene. The authors suggest that the measurement of SCEs induced by diepoxybutane is a possible biomarker of sensitivity to butadiene (106990) genotoxicity and may be effective in occupational epidemiological studies.
NIOSH-Publication; NIOSH-Grant; Cancer; Butadienes; Blood-cells; Chromosome-damage; Occupational-exposure; Epidemiology; DNA-damage; Genotoxic-effects
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Sorsa M; Peltonen K; Vainio H; Hemminki K
Butadiene and styrene: assessment of health hazards
Harvard University, Boston, Massachusetts