HPRT Mutations in Lymphocytes from 1,3-Butadiene-Exposed Workers in China

Abstract

Background1,3-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.ObjectivesIn 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.MethodsSeventy-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.ResultsThe 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).ConclusionsThe 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.

Association between Genetic Polymorphisms of DNA Repair Genes and Chromosomal Damage for 1,3-Butadiene-Exposed Workers in a Matched Study in China

“…Using CBMN cytome assay, our study shows that BD exposure could induce chromosomal damage (MNi and NPBs) in BD-exposed workers, which was consistent with two other studies in China [ 10 , 16 ]. However, several studies have yielded negative results [ 6 – 9 ]. Individual differences especially genetic polymorphisms may contribute such inconsistent results.…”

“…In terms of common genotoxic endpoints, only a few studies have yielded positive results. For example, one group studied the population in Texas in the US and reported significantly elevated frequencies of hypoxanthine-guanine phosphoribosyltransferase ( HPRT ) gene mutations in the peripheral blood lymphocytes (PBLs) of BD-exposed workers [ 5 ], while others failed to find increases in gene mutations [ 6 – 9 ]. For chromosome-level damage, a study in China [ 10 ] indicated positive induction of micronucleus (MN) in the PBLs of heavily exposed BD workers, but similar cytogenetic effects have not been indicated by several studies conducted on BD-exposed workers in Italy and the Czech Republic [ 11 , 12 ].…”

“…Our group has conducted two studies concerning BD-exposed workers in 2002 and 2009, respectively. The 2002 study found that BD exposure did not statistically increase HPRT genes [ 6 ], while the following study conducted in 2009 showed significant chromosomal damage and positive associations with some metabolic genotypes in BD-exposed workers [ 17 ]. The aims of the present study were to determine whether the DNA repair genes ( XRCC1 , MGMT , APE1 , and ADPRT ) can modify the genetic instability induced by BD exposure in current BD workers.…”

The association between genetic damage in peripheral blood lymphocytes and polymorphisms of three glutathione S-transferases in Chinese workers exposed to 1,3-butadiene

“…In China, the annual production volume of BD was over 1.41 million tons in 2008, and was estimated to have reached nearly 2.77 million tons annually by 2012 [2]. BD exposure is a critical public health concern because of its carcinogenicity [1,3,4]. Epidemiological studies have shown that occupational exposure to BD is associated with increased mortality from leukemia [6][7][8] and other hematopoietic malignancies [5].…”

Aliphatic Hydrocarbons

“…In another study in China, a higher but not statistically significant increase in hprt mutation frequencies was observed among petrochemical workers exposed to mean levels of butadiene of 10 ppm. In addition, the frequency of exon deletions in butadiene-exposed workers was significantly higher than that in control subjects (564).…”