Carcinogenesis Advance Access published online on December 8, 2005
Carcinogenesis, doi:10.1093/carcin/bgi297
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 School of Public Health, University of North Carolina, Chapel Hill, NC 27599, USA
* To whom correspondence should be addressed. Although the toxicity of benzene has been linked to its metabolism, the dose-related production of metabolites is not well understood in humans, particularly at low levels of exposure. We investigated unmetabolized benzene in urine (UBz) and all major urinary metabolites [phenol (PH), E,E-muconic acid (MA), hydroquinone (HQ), and catechol (CA)] as well as the minor metabolite, S-phenylmercapturic acid (SPMA), in 250 benzene-exposed workers and 139 control workers in Tianjin, China. Median levels of benzene exposure were about 1.2 ppm for exposed workers (interquartile range: 0.53-3.34 ppm) and 0.005 ppm for control workers (interquartile range: 0.002-0.007 ppm). (Exposures of control workers to benzene were predicted from levels of benzene in their urine). Metabolite production was investigated among groups of 30 workers aggregated by their benzene exposures. We found that the urine concentration of each metabolite was consistently elevated when the group's median benzene exposure was at or above the following air concentrations: 0.2 ppm for MA and SPMA, 0.5 ppm for PH and HQ, and 2 ppm for CA. Dose-related production of the 4 major metabolites and total metabolites (µmol/l per ppm benzene) declined between 2.5 and 26 fold as group median benzene exposures increased between 0.027 and 15.4 ppm. Reductions in metabolite production were most pronounced for CA and PH below one ppm, indicating that metabolism favored production of the toxic metabolites, HQ and MA, at low exposures.
Received August 8, 2005
Revised November 23, 2005
Accepted November 27, 2005
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Using urinary biomarkers to elucidate dose-related patterns of human benzene metabolism
Sungkyoon Kim 1,
Roel Vermeulen 2,
Suramya Waidyanatha 1,
Brent A. Johnson 1,
Qing Lan 2,
Nathaniel Rothman 2,
Martyn T. Smith 3,
Luoping Zhang 3,
Guilan Li 4,
Min Shen 2,
Songnian Yin 4,
and
Stephen M. Rappaport 1 *
2 National Cancer Institute (NCI), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Bethesda, MD 20892, USA
3 School of Public Health, University of California, Berkeley, CA 94720, USA
4 Chinese Center for Disease Control and Prevention, Beijing, China
Stephen M. Rappaport, E-mail: stephen_rappaport{at}unc.edu
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L.-C. Lin, W.-J. Chen, Y.-M. Chiung, T.-S. Shih, and P.-C. Liao Association between GST Genetic Polymorphism and Dose-Related Production of Urinary Benzene Metabolite Markers, trans, trans-Muconic Acid and S-Phenylmercapturic Acid Cancer Epidemiol. Biomarkers Prev., June 1, 2008; 17(6): 1460 - 1469. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Suna, T. Hirao, F. Asakawa, T. Suzue, T. Mannami, and F. Jitsunari Possible sources of urinary benzene among nonoccupationally exposed Japanese subjects Toxicology and Industrial Health, April 1, 2008; 24(3): 155 - 160. [Abstract] [PDF]
|
|
|
|
|
|
S. Kim, R. Vermeulen, S. Waidyanatha, B. A. Johnson, Q. Lan, M. T. Smith, L. Zhang, G. Li, M. Shen, S. Yin, et al. Modeling Human Metabolism of Benzene Following Occupational and Environmental Exposures. Cancer Epidemiol. Biomarkers Prev., November 1, 2006; 15(11): 2246 - 2252. [Abstract] [Full Text] [PDF]
|
|