| HPRT Mutations in Lymphocytes from 1,3-Butadiene-Exposed Workers in China Shengxue Liu,1 Lin Ao,1 Bing Du,2 Yanhong Zhou,1 Jian Yuan,1 Yang Bai,1 Ziyuan Zhou,1 and Jia Cao1 1Department of Hygienic Toxicology, Preventive Medical College, Third Military Medical University, Chongqing, People's Republic of China; 2Institute of Occupational Disease, Yangzi Petrochemical Products Company, Nanjing, People's Republic of China Abstract
Background: 1,3-Butadiene (BD) is an important industrial chemical and an environmental and occupational pollutant. The carcinogenicity of BD in rodents has been proved, but its carcinogenic and mutagenic molecular mechanism(s) are not fully elucidated in humans. Objectives: In the present study, we compared the mutation frequencies and exon deletions of BD-exposed workers with that of control subjects in China to identify the characteristic mutations associated with BD exposure in the human HPRT (hypoxanthine–guanine–phosphoribosyltransferase) gene. Methods: Seventy-four workers exposed to BD via inhalation and 157 matched controls were evaluated in Nanjing, China. Molecular analysis of HPRT mutant T lymphocytes from BD-exposed workers and nonexposed control subjects was conducted to identify changes in the structure of the HPRT gene. A total of 783 HPRT mutants were analyzed by multiplex polymerase chain reaction, in which 368 HPRT mutants were isolated from BD-exposed workers and 415 mutants from control subjects. Results: The BD-exposed workers showed a higher mutation frequency (18.2 ± 9.4  10–6) than the control subjects (12.7 ± 7.3 10–6) , but the difference was not significant (p >0.05) . The frequency of exon deletions in BD-exposed workers (27.4%) was significantly higher than that in control subjects (12.5%) (p < 0.05) , which mainly included multiplex exon deletions (2–8 exons) . Conclusions: The results of the present study suggest that BD should increase the frequency of large deletions of HPRT gene in human lymphocytes This change confirms and supports the previous findings in BD-exposed workers. Key words: 1, 3-butadiene, BD, exon deletion, HPRT gene, lymphocyte, occupational exposure. Environ Health Perspect 116:203–208 (2008) . doi:10.1289/ehp.10353 available via http://dx.doi.org/ [Online 12 November 2007]
Address correspondence to J. Cao, Preventive Medical College, Third Military Medical University, Chongqing 400038, P.R. of China. Telephone: 0086-023-68752271. Fax: 0086-023-68752277. E-mail: caojia@mail.tmmu.com.cn We are grateful to the field collaborators and workers from the Yangzi Petrochemical Products Company for participating in this study. We also thank I-D. Adler from the GSF-National Research Center for Environment and Health, Oberschleissheim, Germany ; G. Cheng from the Department of Biology of the University of Ottawa, Ottawa, Canada ; and R. Zhang from the Department of Pharmacology and Toxicology of the University of Alabama at Birmingham, Birmingham, AL, USA, for their helpful comments. This research was supported by the National Natural Science Foundation of China (No. 39970650, 30100153, and 30471476) and by the National Key Basic Research and Development Program of China (973) (No. 2002CB512901) . B.D. is employeed by the Institute of Occupational Disease, which is part of the Yangzi Petrochemical Co. The Yangzi Petrochemical Co. produces 1,3-butadiene that was used in the work described in this article. All other authors declare no competing financial interest. Received 12 April 2007 ; accepted 11 November 2007.
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