Hematological changes among Chinese workers with a broad range of benzene exposures

Qu, Qingshan; Shore, Roy E.; Li, Guilan; Jin, Ximei; Chen, Lung Chi; Cohen, Beverly S.; Melikian, Assieh A.; Eastmond, David A.; Rappaport, Stephen M.; Yin, Shu; Li, Heyi; Waidyanatha, Suramya; Li, Yuying; Mu, Ruidong; Zhang, Xiaoling; Li, Keqi

doi:10.1002/ajim.10121

Cited by 117 publications

(110 citation statements)

References 12 publications

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“…24 This study found evidence of low-level benzene concentrations having an effect on peripheral blood WBCs. This finding is consistent with other studies conducted in China among shoemakers, [25][26][27] but contrary to a study in the Netherlands. 28 It is possible that the doserelationship between low benzene exposure in exposed workers and the life exposure in internal controls was modified by other factors in the Netherlands study, such as small numbers, worker protection, and life factors (e.g.…”

Section: Discussionsupporting

confidence: 88%

Are polymorphisms in metabolism protective or a risk for reduced white blood cell counts in a Chinese population with low occupational benzene exposures?

Zhang

Huang

et al. 2015

International Journal of Occupational and Environmental Health

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Section: Discussionsupporting

confidence: 88%

Are polymorphisms in metabolism protective or a risk for reduced white blood cell counts in a Chinese population with low occupational benzene exposures?

Zhang

Huang

et al. 2015

International Journal of Occupational and Environmental Health

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“…Although they are also secreted by other cells, platelets remain the most abundant and the most rapidly available source for these CXC-chemokines (17,18). It is well established that benzene lowers peripheral platelet counts (7)(8)(9), raising the possibility that our finding could be explained entirely or in part by a decrease in platelet counts among the exposed subjects. However, we determined that the absolute platelet count did not significantly impact on the difference in expression of PF4 and CTAP-III between benzene exposed and unexposed subjects by using linear regression on the natural logarithm of each protein adjusted and unadjusted for platelet count (Table 3).…”

Section: Confirmation Of Protein Biomarkersmentioning

confidence: 78%

“…Benzene is an established cause of acute myeloid leukemia and myelodysplastic syndromes and may play a role in lymphocytic leukemias and non-Hodgkin lymphoma in humans (1)(2)(3)(4)(5)(6). Additionally, changes in blood and bone marrow consistent with hematotoxicity are recognized in humans and experimental animals (7)(8)(9). Benzene also produces immunosuppressive effects in exposed animals and humans and has been shown to increase susceptibility to tuberculosis and other infectious agents (10,11).…”

mentioning

confidence: 99%

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

Vermeulen¹,

Lan²,

Zhang³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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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 (IMAC3-Cu), and cation exchange (WCX2)]. Protein-expression patterns were detected by surface-enhanced laser desorption͞ 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 ProteinChiparray-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.biomarker ͉ leukemia ͉ mass spectrometry ͉ platelet ͉ molecular epidemiology

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“…O benzeno absorvido é excretado pela via metabólica do ácido mucônico e do fenol, seguida de excreção urinária dos conjugados (sulfatos ou glucuronatos). Exposições humanas de benzeno no ar, em concentrações entre 0,1 e 10 ppm, resultam em perfis de metabólitos urinários com 70-85% de fenol, 5-10% de hidroquinona, 5-10% de ácido trans,trans-mucônico e de catecol e menos de 1% de ácido S-fenilmercaptúrico 6,7 .…”

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Aspectos toxicológicos do benzeno, biomarcadores de exposição e conflitos de interesses

Santos

Figueiredo

Arcuri

et al. 2017

Rev. bras. saúde ocup.

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A despeito do extenso conhecimento produzido sobre a exposição ao benzeno e seus efeitos à saúde, ainda persistem lacunas referentes à sua biotransformação e aos mecanismos que levam à toxicidade por sua ação mutagênica e carcinogênica no organismo.A absorção do benzeno pelo corpo pode ocorrer através da inalação, do contato dérmico e da ingestão. Após a absorção, o benzeno é metabolizado principalmente no fígado (metabolismo primário), com subsequente metabolização na medula óssea (metabolismo secundário) 1 , conforme representado na Figura 1. Os metabólitos produzidos ao final desse processo são excretados pela urina. Na primeira etapa do metabolismo do benzeno ocorre a formação de um intermediário eletrofílico reativo, o benzeno epóxido, sendo catalisada pela enzima citocromo P450 2E1 (CYP2E1), que coexiste em equilíbrio com o seu tautômero c oxepina. Entre as vias que estão envolvidas no metabolismo do óxido de benzeno, a via predominante envolve rearranjo não enzimático para formar fenol. Este é oxidado na presença da enzima CYP2E1, formando catecol e hidroquinona, que, por sua vez, são oxidados na medula óssea, via ação da enzima mieloperoxidase aos metabólitos reativos o-e p-benzoquinona, respectivamente. A reação inversa (redução de o-e p-benzoquinona em catecol e hidroquinona) é catalisada pela enzima NAD(P)H quinona oxidorredutase-1 (NQO1). O catecol e a hidroquinona podem ser convertidos para o metabó-lito 1,2,4-trihidroxibenzeno, através de catálise pela enzima CYP2E1. Alternativamente, o benzeno epóxido pode ser convertido a diidrodiol benzeno e, em seguida, a catecol, sendo essas reações de conversão catalisadas pelas enzimas hidrolase e diidrodiol desidrogenase, respectivamente. Outras vias metabólicas incluem as reações do benzeno epóxido com a glutationa, formando o ácido S-fenilmercaptúrico 2,3 ; e com a CYP2E1, formando a oxepina, a qual sofre reação de abertura do anel, catalisada pelo ferro, produzindo o trans,trans-muconaldeído com subsequente metabolização a ácido trans,trans-mucônico 3,4 . A produção de metabólitos de benzeno primários ocorre principalmente no fígado, via metabolização pela enzima CYP2E1, e também nos pulmões, via reações enzimáticas de CYP2E1, CYP2F1 e CYP2A13. No entanto, reações metabólicas importantes também ocorrem em tecidos-alvo formando compostos altamente reativos como o-e p-benzoquinona, os quais são os possíveis responsáveis pela hematotoxicidade e mielotoxicidade na medula óssea 5 .c Tautômeros têm formas estruturais diferentes e coexistem em equilíbrio químico.

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Hematological changes among Chinese workers with a broad range of benzene exposures

Cited by 117 publications

References 12 publications

Are polymorphisms in metabolism protective or a risk for reduced white blood cell counts in a Chinese population with low occupational benzene exposures?

Are polymorphisms in metabolism protective or a risk for reduced white blood cell counts in a Chinese population with low occupational benzene exposures?

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

Aspectos toxicológicos do benzeno, biomarcadores de exposição e conflitos de interesses

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