Skip to main content
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 1994 Nov;102(Suppl 9):79–85. doi: 10.1289/ehp.94102s979

hprt mutant lymphocyte frequencies in workers at a 1,3-butadiene production plant.

J B Ward Jr 1, M M Ammenheuser 1, W E Bechtold 1, E B Whorton Jr 1, M S Legator 1
PMCID: PMC1566776  PMID: 7698091

Abstract

1,3-Butadiene is a major industrial chemical that has been shown to be a carcinogen at multiple sites in mice and rats at concentrations as low as 6.25 ppm. Occupational exposures have been reduced in response to these findings, but it may not be possible to determine by using traditional epidemiological methods, whether current exposure levels are adequate for protection of worker health. However, it is possible to evaluate the biological significance of exposure to genotoxic chemicals at the time of exposure by measuring levels of genetic damage in exposed populations. We have conducted a pilot study to evaluate the effects of butadiene exposure on the frequencies of lymphocytes containing mutations at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus in workers in a butadiene production plant. At the same time, urine specimens from the same individuals were collected and evaluated for the presence of butadiene-specific metabolites. Eight workers from areas of the plant where the highest exposures to butadiene occur were compared to five workers from plant areas where butadiene exposures were low. In addition, six subjects with no occupational exposure to butadiene were also studied as outside controls. All of the subjects were nonsmokers. An air sampling survey conducted for 6 months, and ending about 3 months before the study, indicated that average butadiene levels in the air of the high-exposure areas were about 3.5 +/- 7.5 ppm. They were 0.03 +/- 0.03 ppm in the low-exposure areas. Peripheral blood lymphocytes from the subjects were assayed using an autoradiographic test for hprt mutations.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
82

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abelson P. H. Exaggerated carcinogenicity of chemicals. Science. 1992 Jun 19;256(5064):1609–1609. doi: 10.1126/science.256.5064.1609. [DOI] [PubMed] [Google Scholar]
  2. Albertini R. J., Nicklas J. A., O'Neill J. P., Robison S. H. In vivo somatic mutations in humans: measurement and analysis. Annu Rev Genet. 1990;24:305–326. doi: 10.1146/annurev.ge.24.120190.001513. [DOI] [PubMed] [Google Scholar]
  3. Albertini R. J. Somatic gene mutations in vivo as indicated by the 6-thioguanine-resistant T-lymphocytes in human blood. Mutat Res. 1985 Jun-Jul;150(1-2):411–422. doi: 10.1016/0027-5107(85)90138-1. [DOI] [PubMed] [Google Scholar]
  4. Albertini R. J., Sullivan L. M., Berman J. K., Greene C. J., Stewart J. A., Silveira J. M., O'Neill J. P. Mutagenicity monitoring in humans by autoradiographic assay for mutant T lymphocytes. Mutat Res. 1988 Mar;204(3):481–492. doi: 10.1016/0165-1218(88)90043-2. [DOI] [PubMed] [Google Scholar]
  5. Ammenheuser M. M., Au W. W., Whorton E. B., Jr, Belli J. A., Ward J. B., Jr Comparison of hprt variant frequencies and chromosome aberration frequencies in lymphocytes from radiotherapy and chemotherapy patients: a prospective study. Environ Mol Mutagen. 1991;18(2):126–135. doi: 10.1002/em.2850180208. [DOI] [PubMed] [Google Scholar]
  6. Ammenheuser M. M., Berenson A. B., Stiglich N. J., Whorton E. B., Jr, Ward J. B., Jr Elevated frequencies of hprt mutant lymphocytes in cigarette-smoking mothers and their newborns. Mutat Res. 1994 Jan 16;304(2):285–294. doi: 10.1016/0027-5107(94)90221-6. [DOI] [PubMed] [Google Scholar]
  7. Ammenheuser M. M., Ward J. B., Jr, Whorton E. B., Jr, Killian J. M., Legator M. S. Elevated frequencies of 6-thioguanine-resistant lymphocytes in multiple sclerosis patients treated with cyclophosphamide: a prospective study. Mutat Res. 1988 Mar;204(3):509–520. doi: 10.1016/0165-1218(88)90045-6. [DOI] [PubMed] [Google Scholar]
  8. Arce G. T., Vincent D. R., Cunningham M. J., Choy W. N., Sarrif A. M. In vitro and in vivo genotoxicity of 1,3-butadiene and metabolites. Environ Health Perspect. 1990 Jun;86:75–78. doi: 10.1289/ehp.908675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Compton P. J., Hooper K., Smith M. T. Human somatic mutation assays as biomarkers of carcinogenesis. Environ Health Perspect. 1991 Aug;94:135–141. doi: 10.1289/ehp.94-1567966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Conner M. K., Luo J. E., Gutierrez de Gotera O. Induction and rapid repair of sister-chromatid exchanges in multiple murine tissues in vivo by diepoxybutane. Mutat Res. 1983 Mar;108(1-3):251–263. doi: 10.1016/0027-5107(83)90124-0. [DOI] [PubMed] [Google Scholar]
  11. Cunningham M. J., Choy W. N., Arce G. T., Rickard L. B., Vlachos D. A., Kinney L. A., Sarrif A. M. In vivo sister chromatid exchange and micronucleus induction studies with 1,3-butadiene in B6C3F1 mice and Sprague-Dawley rats. Mutagenesis. 1986 Nov;1(6):449–452. [PubMed] [Google Scholar]
  12. Dahl A. R., Bechtold W. E., Bond J. A., Henderson R. F., Mauderly J. L., Muggenburg B. A., Sun J. D., Birnbaum L. S. Species differences in the metabolism and disposition of inhaled 1,3-butadiene and isoprene. Environ Health Perspect. 1990 Jun;86:65–69. doi: 10.1289/ehp.908665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dahl A. R., Sun J. D., Birnbaum L. S., Bond J. A., Griffith W. C., Jr, Mauderly J. L., Muggenburg B. A., Sabourin P. J., Henderson R. F. Toxicokinetics of inhaled 1,3-butadiene in monkeys: comparison to toxicokinetics in rats and mice. Toxicol Appl Pharmacol. 1991 Aug;110(1):9–19. doi: 10.1016/0041-008x(91)90285-m. [DOI] [PubMed] [Google Scholar]
  14. Dankovic D. A., Stayner L. T., Smith R. J., Bailer A. J. Carcinogenicity of butadiene. Science. 1992 Sep 4;257(5075):1330–1331. doi: 10.1126/science.1529327. [DOI] [PubMed] [Google Scholar]
  15. De Flora S. Development and application of biomarkers exploitable for human exposure monitoring. Teratog Carcinog Mutagen. 1990;10(3):211–214. doi: 10.1002/tcm.1770100303. [DOI] [PubMed] [Google Scholar]
  16. Divine B. J. An update on mortality among workers at a 1,3-butadiene facility--preliminary results. Environ Health Perspect. 1990 Jun;86:119–128. doi: 10.1289/ehp.9086119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Downs T. D., Crane M. M., Kim K. W. Mortality among workers at a butadiene facility. Am J Ind Med. 1987;12(3):311–329. doi: 10.1002/ajim.4700120307. [DOI] [PubMed] [Google Scholar]
  18. Fajen J. M., Roberts D. R., Ungers L. J., Krishnan E. R. Occupational exposure of workers to 1,3-butadiene. Environ Health Perspect. 1990 Jun;86:11–18. doi: 10.1289/ehp.908611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Fearon E. R., Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990 Jun 1;61(5):759–767. doi: 10.1016/0092-8674(90)90186-i. [DOI] [PubMed] [Google Scholar]
  20. Irons R. D., Oshimura M., Barrett J. C. Chromosome aberrations in mouse bone marrow cells following in vivo exposure to 1,3-butadiene. Carcinogenesis. 1987 Nov;8(11):1711–1714. doi: 10.1093/carcin/8.11.1711. [DOI] [PubMed] [Google Scholar]
  21. Landrigan P. J. Carcinogenicity of butadiene. Science. 1992 Sep 4;257(5075):1330–1331. doi: 10.1126/science.1482491. [DOI] [PubMed] [Google Scholar]
  22. Landrigan P. J. Critical assessment of epidemiologic studies on the human carcinogenicity of 1,3-butadiene. Environ Health Perspect. 1990 Jun;86:143–147. doi: 10.1289/ehp.9086143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lemen R. A., Meinhardt T. J., Crandall M. S., Fajen J. M., Brown D. P. Environmental epidemiologic investigations in the styrene-butadiene rubber production industry. Environ Health Perspect. 1990 Jun;86:103–106. doi: 10.1289/ehp.9086103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Matanoski G. M., Santos-Burgoa C., Schwartz L. Mortality of a cohort of workers in the styrene-butadiene polymer manufacturing industry (1943-1982). Environ Health Perspect. 1990 Jun;86:107–117. doi: 10.1289/ehp.9086107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Melnick R. L., Huff J., Chou B. J., Miller R. A. Carcinogenicity of 1,3-butadiene in C57BL/6 x C3H F1 mice at low exposure concentrations. Cancer Res. 1990 Oct 15;50(20):6592–6599. [PubMed] [Google Scholar]
  26. Mendelsohn M. L. New approaches for biological monitoring of radiation workers. Health Phys. 1990 Jul;59(1):23–28. doi: 10.1097/00004032-199007000-00002. [DOI] [PubMed] [Google Scholar]
  27. Morrow N. L. The industrial production and use of 1,3-butadiene. Environ Health Perspect. 1990 Jun;86:7–8. doi: 10.1289/ehp.90867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. O'Neill J. P., McGinniss M. J., Berman J. K., Sullivan L. M., Nicklas J. A., Albertini R. J. Refinement of a T-lymphocyte cloning assay to quantify the in vivo thioguanine-resistant mutant frequency in humans. Mutagenesis. 1987 Mar;2(2):87–94. doi: 10.1093/mutage/2.2.87. [DOI] [PubMed] [Google Scholar]
  29. O'Neill J. P., Sullivan L. M., Booker J. K., Pornelos B. S., Falta M. T., Greene C. J., Albertini R. J. Longitudinal study of the in vivo hprt mutant frequency in human T-lymphocytes as determined by a cell cloning assay. Environ Mol Mutagen. 1989;13(4):289–293. doi: 10.1002/em.2850130403. [DOI] [PubMed] [Google Scholar]
  30. Owen P. E., Glaister J. R. Inhalation toxicity and carcinogenicity of 1,3-butadiene in Sprague-Dawley rats. Environ Health Perspect. 1990 Jun;86:19–25. doi: 10.1289/ehp.908619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sabourin P. J., Burka L. T., Bechtold W. E., Dahl A. R., Hoover M. D., Chang I. Y., Henderson R. F. Species differences in urinary butadiene metabolites; identification of 1,2-dihydroxy-4-(N-acetylcysteinyl)butane, a novel metabolite of butadiene. Carcinogenesis. 1992 Sep;13(9):1633–1638. doi: 10.1093/carcin/13.9.1633. [DOI] [PubMed] [Google Scholar]
  32. Sasiadek M., Järventaus H., Sorsa M. Sister-chromatid exchanges induced by 1.3-butadiene and its epoxides in CHO cells. Mutat Res. 1991 May;263(1):47–50. doi: 10.1016/0165-7992(91)90033-z. [DOI] [PubMed] [Google Scholar]
  33. Sasiadek M., Norppa H., Sorsa M. 1,3-Butadiene and its epoxides induce sister-chromatid exchanges in human lymphocytes in vitro. Mutat Res. 1991 Oct;261(2):117–121. doi: 10.1016/0165-1218(91)90057-s. [DOI] [PubMed] [Google Scholar]
  34. Sharief Y., Brown A. M., Backer L. C., Campbell J. A., Westbrook-Collins B., Stead A. G., Allen J. W. Sister chromatid exchange and chromosome aberration analyses in mice after in vivo exposure to acrylonitrile, styrene, or butadiene monoxide. Environ Mutagen. 1986;8(3):439–448. doi: 10.1002/em.2860080312. [DOI] [PubMed] [Google Scholar]
  35. Strauss G. H., Albertini R. J. Enumeration of 6-thioguanine-resistant peripheral blood lymphocytes in man as a potential test for somatic cell mutations arising in vivo. Mutat Res. 1979 Jul;61(2):353–379. doi: 10.1016/0027-5107(79)90140-4. [DOI] [PubMed] [Google Scholar]
  36. Tice R. R., Boucher R., Luke C. A., Shelby M. D. Comparative cytogenetic analysis of bone marrow damage induced in male B6C3F1 mice by multiple exposures to gaseous 1,3-butadiene. Environ Mutagen. 1987;9(3):235–250. doi: 10.1002/em.2860090303. [DOI] [PubMed] [Google Scholar]
  37. Ward J. B., Jr, Ammenheuser M. M., Ramanujam V. M., Morris D. L., Whorton E. B., Jr, Legator M. S. The mutagenic effects of low level sub-acute inhalation exposure to benzene in CD-1 mice. Mutat Res. 1992 Jul;268(1):49–57. doi: 10.1016/0027-5107(92)90082-d. [DOI] [PubMed] [Google Scholar]
  38. de Meester C. Genotoxic properties of 1,3-butadiene. Mutat Res. 1988 May;195(3):273–281. doi: 10.1016/0165-1110(88)90005-x. [DOI] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES