Grant Number:	5R01CA069463-04 Interpret this number
Primary Investigator:	Rappaport, Stephen
Organization:	University Of N Carolina At Chapel Hill
Project Title:	Biomarkers of Styrene Oxide
Fiscal Year:	1998

Preliminary evidence is presented that exposures to the carcinogen, styrene-7,8-oxide (SO), which arise from reactions of styrene during the production of reinforced plastics, cause significant increases of SO biomarkers [adducts of SO with DNA and serum albumin and sister-chromatid exchanges] in workers. This finding is remarkable because coexposure to styrene at levels of 400 times those of SO results in only minor (if any) production of these same SO-biomarkers, despite the conversion of virtually all styrene to SO by the human liver. The proposed study is intended to determine the relative contributions of inhaled styrene and SO to the integrated dose of SO in the blood of workers in the reinforced plastics industry. To achieve this goal, we will recruit 100 workers within 17 facilities in the reinforced plastics industry. We will measure the airborne exposures of each worker to styrene and SO twice during one year. Blood samples will also be collected during each survey so that we can measure the Concentrations of styrene and SO in the blood as well as the levels of SO-adducts of albumin, Hb, and lymphocyte DNA. These data will not only allow us to determine the relative contributions of styrene and SO to the integrated dose of SO in the blood, but also to address the following issues: 1) to validate the use of protein adducts to estimate the integrated dose of SO in blood, 2) to compare DNA adducts of SO measured by high-resolution mass spectrometry (N-7 adducts of guanine) with those measured by 32P-postlabeling (N2 adducts of guanine), and 3) to determine the relationships among the protein and DNA adducts of SO. Three secondary goals of the investigation will also be pursued. First, we will determine how factors related to the formulation and use of reinforced plastics affect exposures to styrene and SO. This will be accomplished by gathering information during each survey regarding formulations of resins as well as the jobs and tasks of individual workers and then determining the contributions of these factors on exposure to styrene and SO. Second, we will determine whether SO per se is the source of background adducts of SO in human blood by employing ultratrace analyses of SO in the blood of 100 persons without occupational exposures to styrene or to SO. Protein and DNA adducts will also be measured in these persons to allow us to compare background adduct levels with those of SO in blood. Third, we will determine whether workers with relatively low levels of SO-DNA adducts show greater expression of the DNA repair system, N-methylpurine-DNA glycosylase, than workers with relatively high levels of SO-DNA adducts.




Variability of albumin adducts of 1,4-benzoquinone, a toxic metabolite of benzene, in human volunteers.
Authors: Lin Y.S. , McKelvey W. , Waidyanatha S. , Rappaport S.M. .
Source: Biomarkers : Biochemical Indicators Of Exposure, Response, And Susceptibility To Chemicals, 2006 Jan-Feb; 11(1), p. 14-27.
PMID: 16484134
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Physiological modeling of the relative contributions of styrene-7,8-oxide derived from direct inhalation and from styrene metabolism to the systemic dose in humans.
Authors: Tornero-Velez R. , Rappaport S.M. .
Source: Toxicological Sciences : An Official Journal Of The Society Of Toxicology, 2001 Dec; 64(2), p. 151-61.
PMID: 11719697
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Determination of styrene and styrene-7,8-oxide in human blood by gas chromatography-mass spectrometry.
Authors: Tornero-Velez R. , Waidyanatha S. , Pérez H.L. , Osterman-Golkar S. , Echeverria D. , Rappaport S.M. .
Source: Journal Of Chromatography. B, Biomedical Sciences And Applications, 2001-06-05 00:00:00.0; 757(1), p. 59-68.
PMID: 11419749
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Measurement of styrene-7,8-oxide and other oxidation products of styrene in air.
Authors: Tornero-Velez R. , Waidyanatha S. , Echeverria D. , Rappaport S.M. .
Source: Journal Of Environmental Monitoring : Jem, 2000 Apr; 2(2), p. 111-7.
PMID: 11253028
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Protein adducts as dosimeters of human exposure to styrene, styrene-7,8-oxide, and benzene.
Authors: Rappaport S.M. , Yeowell-O'Connell K. .
Source: Toxicology Letters, 1999-09-05 00:00:00.0; 108(2-3), p. 117-26.
PMID: 10511253
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An investigation of factors contributing to styrene and styrene-7,8-oxide exposures in the reinforced-plastics industry.
Authors: Nylander-French L.A. , Kupper L.L. , Rappaport S.M. .
Source: The Annals Of Occupational Hygiene, 1999 Feb; 43(2), p. 99-105.
PMID: 10206038
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Comparison of styrene-7,8-oxide adducts formed via reaction with cysteine, N-terminal valine and carboxylic acid residues in human, mouse and rat hemoglobin.
Authors: Yeowell-O'Connell K. , Pauwels W. , Severi M. , Jin Z. , Walker M.R. , Rappaport S.M. , Veulemans H. .
Source: Chemico-biological Interactions, 1997-08-29 00:00:00.0; 106(1), p. 67-85.
PMID: 9305409
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