© 1995 Oxford University Press
research-article |
Mechanistic data indicate that 1,3-butadiene is a human carcinogen
Environmental Carcingenesis Program and Laboratory of Quantitative and Computational Biology, National Institute of Environmental Health Sciences Research Triangle Park, North carolina 27709, USA
1 To whom correspondence should be addressed
A review of the epidemiological and mechanistic data on 1,3-butadiene indicates that this chemical is a human carcinogen for which the mouse is a human carcinogen for which the mouse is an appropriate model for assessing human cancer risk. Butadiene is carcinogenic at multiple organ sites in laboratory animals, including the induction of lymphomas in mice, while epidemiological studies have consistently found associations between occupational exposure to butadiene and increased mortality from lymphatic and hematopoietic cancers. Activated oncogenes and inactivated tumor suppressor genes in butadieneinduced tumors in mice are analogous to genetic alterations frequently observed in human cancers. Butadiene is metabolized to mutagenic and carcinogenic epoxides in all mammalian species studied, including humans. These metabolites form N7-alkylguanine adducts which have been detected in liver DNA of mice exposed to butadiene and in urine of exposed workers. Increases in hprt mutations were observed in lymphocytes from mice exposed to butadiene and in occupationally exposed humans. The mutational spectra for butadiene and its epoxide metabolites at the hprt locus in mouse lymphocytes are similar to the mutational spectrum of ethylene oxide; all of these chemicals exhibit a high percentage of frameshift mutations. Ethylene oxide, an alkylating agent that also forms an N7-alkylguanine adduct, was recently classified by the International Agency for Research on Cancer as a human carcinogen. Based on these data, we suggest that cancer induction by ethylene oxide and butadiene involve similar molecular mechanisms.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  E G Knox Childhood cancers and atmospheric carcinogens J Epidemiol Community Health, February 1, 2005; 59(2): 101 - 105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Kemper, R. J. Krause, and A. A. Elfarra Metabolism of Butadiene Monoxide by Freshly Isolated Hepatocytes from Mice and Rats: Different Partitioning between Oxidative, Hydrolytic, and Conjugation Pathways Drug Metab. Dispos., June 1, 2001; 29(6): 830 - 836. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. Z. Abdel-Rahman, M. M. Ammenheuser, and J. B. Ward Jr Human sensitivity to 1,3-butadiene: role of microsomal epoxide hydrolase polymorphisms Carcinogenesis, March 1, 2001; 22(3): 415 - 423. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-H. L. Hong, T. R. Devereux, R. L. Melnick, C. R. Moomaw, G. A. Boorman, and R. C. Sills Mutations of ras Protooncogenes and p53 Tumor Suppressor Gene in Cardiac Hemangiosarcomas from B6C3F1 Mice Exposed to 1,3-Butadiene for 2 Years Toxicol Pathol, July 1, 2000; 28(4): 529 - 534. [Abstract] [PDF]
|
|
|
|
|
|
R.B. Hayes, L. Zhang, S. Yin, J.A. Swenberg, L. Xi, J. Wiencke, W.E. Bechtold, M. Yao, N. Rothman, R. Haas, et al. Genotoxic markers among butadiene polymer workers in China Carcinogenesis, January 1, 2000; 21(1): 55 - 62. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.n. Murg, M. Schuler, and D.A. Eastmond Evaluation of micronuclei and chromosomal breakage in the 1cen-q12 region by the butadiene metabolites epoxybutene and diepoxybutane in cultured human lymphocytes Mutagenesis, November 1, 1999; 14(6): 541 - 546. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Buckley, D. P. Coleman, J. P. Burgess, B. F. Thomas, L. T. Burka, and A. R. Jeffcoat Identification of Urinary Metabolites of Isoprene in Rats and Comparison with Mouse Urinary Metabolites Drug Metab. Dispos., July 1, 1999; 27(7): 848 - 854. [Abstract] [Full Text]
|
|
|
|
|
|
R. L. Melnick, R. C. Sills, C. J. Portier, J. H. Roycroft, B. J. Chou, S. L. Grumbein, and R. A. Miller Multiple organ carcinogenicity of inhaled chloroprene (2-chloro-1,3-butadiene) in F344/N rats and B6C3F1 mice and comparison of dose–response with 1,3-butadiene in mice Carcinogenesis, May 1, 1999; 20(5): 867 - 878. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Kemper, A. A. Elfarra, and S. R. Myers Metabolism of 3-Butene-1,2-diol in B6C3F1 Mice. Evidence for Involvement of Alcohol Dehydrogenase and Cytochrome P450 Drug Metab. Dispos., September 1, 1998; 26(9): 914 - 920. [Abstract] [Full Text]
|
|
|
|
|
|
R.R. Maronpot and G.A. Boorman The Contribution of the Mouse in Hazard Identification Studies Toxicol Pathol, November 1, 1996; 24(6): 726 - 731. [Abstract] [PDF]
|
|