A new biomarker of carcinogen sensitivity has been developed that is rapid, inexpensive and applicable to molecular epidemiologic studies of human carcinogenesis. This marker of carcinogen sensitivity is based on the detection of increased induction of sister chromatid exchanges (SCEs) in peripheral blood lymphocytes by the potent carcinogen and known metabolite of 1,3-butadiene, diepoxybutane (DEB). Two cross-sectional studies indicated that the marker is present in 24% of apparently normal individuals, and a pilot twin study indicated that the marker is influenced by familial factors. Lymphocytes from marker positive persons contained an increase in """"""""spontaneous"""""""" SCE frequencies, perhaps evidence of chromosomal instability in these individuals. SCE rates were further increased by cigarette smoking in marker positive subjects. Direct exposure to DEB in humans is rare, but exposure does exist in occupational groups who work in 1,3-butadiene (BD) production and use because BD is metabolized to DEB. In the present study I propose to extend this research in an applied study of chromosomal sensitivity to occupational exposure to BD in members of the Oil, Chemical, and Atomic Workers Union (OCAW) in Port Neches, Texas. I propose to define the extent of the genotoxicity induced by workplace exposure to BD, documenting this in humans for the first time. I hypothesize that the DEB sensitivity marker status interacts with occupational 1,3-butadiene exposure in the production of chromosomal damage in peripheral blood lymphocytes. By estimating exposures to BD, I will test whether the DEB sensitivity marker is associated with enhancement of BD-induced chromosome damage in high-, medium- and low-exposed workers, compared with control, non-BD-exposed OCAW members. The goal of this SERCA is to initiate applied studies of union workers exposed to BD in an effort to define the genotoxicity of BD exposure in humans and to determine further if there are workers who are hypersusceptible to BD-induced chromosome damage and thereby, possibly hypersusceptible to BD-induced cancers.
