Molecular analysis of
            <i>hprt</i>
            mutant lymphocytes from 1,3‐butadiene–exposed workers

Ma, Hongbao; Wood, Thomas G.; Ammenheuser, Marinel M.; Rosenblatt, Judah; Ward, Jonathan B.

doi:10.1002/1098-2280(2000)36:1<59::aid-em9>3.0.co;2-#

Cited by 24 publications

(6 citation statements)

References 51 publications

(48 reference statements)

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“…The increase appeared to be primarily the result of an increase in multiple exon deletions ( p < 0.05), including both continuous deletions and discontinuous deletions ( Table 4 ). Our results are in agreement with the data from Ma et al (2000) , Burkhart-Schultz and Jones (1997) , and Burkhart-Schultz et al (1996) . Analysis of the in vitro mutational spectra of DEB- and EB-induced mutants in a study by Steen et al (1997a , 1997b) clearly revealed that a decrease in the proportion of single-base substitutions was associated with an increase in the proportion of large deletion mutations Our data and similar findings by Meng et al (2004) indicate that it is not necessary to invoke the formation of DEB as the sole source of large exon deletions; rather, HPRT spectra data from rats indicate that EB-diol is a likely source of deletion mutations.…”

Section: Discussionsupporting

confidence: 92%

“…Thus, we suppose that the increases of exon deletions in the mutants from exposed workers likely represent the mutations induced by BD. In a previous study Ma et al (2000) further used HPRT coding sequence analysis and compared the molecular mutational spectrum of BD-exposed workers with those of control subjects. The authors identified a lower frequency of single-base substitutions, a higher proportion of A:T → T:A transversions and ± 1 frameshift mutations in BD-exposed workers.…”

Section: Discussionmentioning

confidence: 99%

“…We selected the T-cell cloning assay as the HPRT mutation assay for our study; the method has been described previously ( Ma et al 2000 ). Briefly, Ficoll reagent (Haoyang Biological Manufacture Co., Tianjin, China) was used to isolate the peripheral lymphocytes from whole blood by density centrifugation.…”

Section: Methodsmentioning

confidence: 99%

“…All wells of an expanded mutant clone were pooled and harvested for the isolation of DNA. A wizard genomic DNA purification kit (Promega Corp., Madison, WI, USA) was used to isolate DNA from cells; the isolation was performed according to the procedure of Ma et al (2000) . Simultaneously, normal lymphocytes were collected to isolate DNA to serve as controls for the further molecular analysis.…”

Section: Methodsmentioning

confidence: 99%

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

Liu

Du³

et al. 2008

Environ Health Perspect

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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.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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

Liu

Du³

et al. 2008

Environ Health Perspect

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“…PAHs are the main carcinogens that produce G→T mutations 25,49 . NNK may induce both G→T and G→A mutations 50 , and 4aminobiphenyl and 1,3-butadiene cause the A→T transversions [51][52][53] . Other smohaze carcinogens also induce characteristic nucleotide substitutions in the genome 54 .…”

Section: Genomic Mutations Carcinogens and Nucleotide Substitutionsmentioning

confidence: 99%

Tobacco, air pollution, environmental carcinogenesis, and thoughts on conquering strategies of lung cancer

Zhou

2019

Cancer Biol Med

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Each year there will be an estimated 2.1 million new lung cancer cases and 1.8 million lung cancer deaths worldwide. Tobacco smoke is the No.1 risk factors of lung cancer, accounting for > 85% lung cancer deaths. Air pollution, or haze, comprises ambient air pollution and household air pollution, which are reported to cause 252,000 and 304,000 lung cancer deaths each year, respectively. Tobacco smoke and haze (hereafter, smohaze) contain fine particles originated from insufficient combustion of biomass or coal, have quite similar carcinogens, and cause similar diseases. Smohaze exert hazardous effects on exposed populations, including induction of a large amount of mutations in the genome, alternative splicing of mRNAs, abnormalities in epigenomics, initiation of tumor-promoting chronic inflammation, and facilitating immune escape of transformed cells. Tackling smohaze and development of multi-targets-based preventive and therapeutic approaches targeting smohaze-induced carcinogenesis are the key to conquer lung cancer in the future.

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A model of sensitivity: 1,3‐butadiene increases mutant frequencies and genomic damage in mice lacking a functional microsomal epoxide hydrolase gene

Wickliffe

Ammenheuser

Salazar

et al. 2003

Environ and Mol Mutagen

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The specific role that polymorphisms in xenobiotic metabolizing enzymes play in modulating sensitivity to 1,3-butadiene (BD) genotoxicity has been relatively unexplored. The enzyme microsomal epoxide hydrolase (mEH) is important in detoxifying the mutagenic epoxides of BD (butadiene monoepoxide [BDO], butadiene diepoxide [BDO(2)]). Polymorphisms in the human mEH gene appear to affect the function of the enzyme. We exposed mice with normal mEH activity (WT) and knockout mice without mEH activity (KO) to 20 ppm BD (inhalation) or 30 mg/kg BDO(2) (intraperitoneal [IP] injection). We then compared Hprt mutant frequencies (MFs) among these groups. KO mice exposed to BD exhibited a significant (P < 0.05) 12.4-fold increase in MF over controls and a significant 5.4-fold increase in MF over exposed WT mice. Additionally, KO mice exposed to BDO(2) exhibited a significant 4.5-fold increase in MF over controls and a significant 1.7-fold increase in MF over exposed WT mice. We also compared genomic damage in WT and KO mice (comet tail moment) following IP exposure to 3 mg/kg and 30 mg/kg BDO(2). KO mice exposed to 3 mg/kg exhibited significantly more DNA damage than controls (7.5-12.1-fold increase) and exposed WT mice (3 mg/kg; 4.8-fold increase). KO mice exposed to 30 mg/kg BDO(2) exhibited significantly more DNA damage than all other groups (2.3-27.9-fold increase). Correlation analysis indicated that a significant, positive relationship (r(2) = 0.92) exists between comet-measured damage and Hprt MFs. The lack of mEH activity increases the genetic sensitivity of mice exposed to BD and BDO(2). This model should facilitate a mechanistic understanding of the observed variation in human genetic sensitivity following exposure to BD.

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Molecular analysis of hprt mutant lymphocytes from 1,3‐butadiene–exposed workers

Cited by 24 publications

References 51 publications

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

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

Tobacco, air pollution, environmental carcinogenesis, and thoughts on conquering strategies of lung cancer

A model of sensitivity: 1,3‐butadiene increases mutant frequencies and genomic damage in mice lacking a functional microsomal epoxide hydrolase gene

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