Decreased levels of CXC-chemokines in serum of benzene-exposed workers identified by array-based proteomics

Roel Vermeulen, Qing Lan, Luoping Zhang, Laura Gunn, Diane McCarthy, Ronald L. Woodbury, Marielena McGuire, Vladimir N. Podust, Guilan Li, Nilanjan Chatterjee, Ruidong Mu, Songnian Yin, Nathaniel Rothman, Martyn T. Smith

Research output: Contribution to journalArticle

Abstract

Benzene is an important industrial chemical and environmental contaminant that causes leukemia. To obtain mechanistic insight into benzene's mechanism of action, we examined the impact of benzene on the human serum proteome in a study of exposed healthy shoe-factory workers and unexposed controls. Two sequential studies were performed, each using sera from 10 workers exposed to benzene (overall mean benzene air level > 30 ppm) and 10 controls. Serum samples were subjected to anion-exchange fractionation and bound to three types of ProteinChip arrays (Ciphergen Biosystems, Fremont, CA) [hydrophobic (H50), metal affinity (IMACB-Cu), and cation exchange (WCX2)]. Protein-expression patterns were detected by surface-enhanced laser desorption/ ionization (SELDI)-TOF MS. Three proteins (4.1, 7.7, and 9.3 kDa) were consistently down-regulated in exposed compared with control subjects in both studies. All proteins were highly inversely correlated with individual estimates of benzene exposure (r > 0.75). The 7.7- and 9.3-kDa proteins were subsequently identified as platelet factor (PF)4 and connective tissue activating peptide (CTAP)-III. Initial proteomic results for PF4 and CTAP-III were subsequently confirmed in a single experiment using a ProteinChip-array-based immunoassay(Ciphergen Biosystems). The altered expression of the platelet-derived CXC-chemokines (40% and 63% for PF4 and CTAP-III, respectively) could not be explained by changes in absolute platelet counts. Thus, SELDI-TOF analysis of a limited number of exposed and unexposed subjects revealed that lowered expression of PF4 and CTAP-III proteins is a potential biomarker of benzene's early biologic effects and may play a role in the immunosuppressive effects of benzene.

Original languageEnglish (US)
Pages (from-to)17041-17046
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number47
DOIs
StatePublished - Nov 22 2005
Externally publishedYes

Fingerprint

CXC Chemokines
Benzene
Proteomics
Serum
Protein Array Analysis
Proteins
Lasers
Platelet Factor 4
Shoes
Proteome
Immunosuppressive Agents
Platelet Count
Immunoassay
Anions
Cations
Leukemia
Blood Platelets
Biomarkers
Metals
Air

Keywords

  • Biomarker
  • Leukemia
  • Mass spectrometry
  • Molecular epidemiology
  • Platelet

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Decreased levels of CXC-chemokines in serum of benzene-exposed workers identified by array-based proteomics. / Vermeulen, Roel; Lan, Qing; Zhang, Luoping; Gunn, Laura; McCarthy, Diane; Woodbury, Ronald L.; McGuire, Marielena; Podust, Vladimir N.; Li, Guilan; Chatterjee, Nilanjan; Mu, Ruidong; Yin, Songnian; Rothman, Nathaniel; Smith, Martyn T.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 47, 22.11.2005, p. 17041-17046.

Research output: Contribution to journalArticle

Vermeulen, R, Lan, Q, Zhang, L, Gunn, L, McCarthy, D, Woodbury, RL, McGuire, M, Podust, VN, Li, G, Chatterjee, N, Mu, R, Yin, S, Rothman, N & Smith, MT 2005, 'Decreased levels of CXC-chemokines in serum of benzene-exposed workers identified by array-based proteomics', Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 47, pp. 17041-17046. https://doi.org/10.1073/pnas.0508573102
Vermeulen, Roel ; Lan, Qing ; Zhang, Luoping ; Gunn, Laura ; McCarthy, Diane ; Woodbury, Ronald L. ; McGuire, Marielena ; Podust, Vladimir N. ; Li, Guilan ; Chatterjee, Nilanjan ; Mu, Ruidong ; Yin, Songnian ; Rothman, Nathaniel ; Smith, Martyn T. / Decreased levels of CXC-chemokines in serum of benzene-exposed workers identified by array-based proteomics. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 47. pp. 17041-17046.
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AU - Woodbury, Ronald L.

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N2 - Benzene is an important industrial chemical and environmental contaminant that causes leukemia. To obtain mechanistic insight into benzene's mechanism of action, we examined the impact of benzene on the human serum proteome in a study of exposed healthy shoe-factory workers and unexposed controls. Two sequential studies were performed, each using sera from 10 workers exposed to benzene (overall mean benzene air level > 30 ppm) and 10 controls. Serum samples were subjected to anion-exchange fractionation and bound to three types of ProteinChip arrays (Ciphergen Biosystems, Fremont, CA) [hydrophobic (H50), metal affinity (IMACB-Cu), and cation exchange (WCX2)]. Protein-expression patterns were detected by surface-enhanced laser desorption/ ionization (SELDI)-TOF MS. Three proteins (4.1, 7.7, and 9.3 kDa) were consistently down-regulated in exposed compared with control subjects in both studies. All proteins were highly inversely correlated with individual estimates of benzene exposure (r > 0.75). The 7.7- and 9.3-kDa proteins were subsequently identified as platelet factor (PF)4 and connective tissue activating peptide (CTAP)-III. Initial proteomic results for PF4 and CTAP-III were subsequently confirmed in a single experiment using a ProteinChip-array-based immunoassay(Ciphergen Biosystems). The altered expression of the platelet-derived CXC-chemokines (40% and 63% for PF4 and CTAP-III, respectively) could not be explained by changes in absolute platelet counts. Thus, SELDI-TOF analysis of a limited number of exposed and unexposed subjects revealed that lowered expression of PF4 and CTAP-III proteins is a potential biomarker of benzene's early biologic effects and may play a role in the immunosuppressive effects of benzene.

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