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Essential and Non-essential Metals pp 143–180Cite as

Molecular Mechanisms of Chromium-Induced Carcinogenesis

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Part of the book series: Molecular and Integrative Toxicology ((MOLECUL))

Abstract

Hexavalent chromium (Cr(VI)) has been utilized for industrial applications for over 200 years. Due to its frequent use, workers in over 80 different industries are exposed to Cr(VI). Epidemiological studies indicate particulate Cr(VI) compounds are the most potent carcinogens, resulting in sinusoid and lung tumors following inhalation. Although Cr(VI) is well established as a human lung carcinogen, the mechanism of carcinogenesis remains unknown. Here, we examine the results of Cr(VI)-induced tumor, in vivo, cell culture, and in vitro studies in the context of three major models of carcinogenesis: multistage carcinogenesis, genomic instability, and epigenetic modification. A wealth of data support the conclusion that genomic instability is a driving mechanism of Cr(VI)-induced carcinogenesis. However, recent studies suggest epigenetic modifications also play a crucial role in its carcinogenic mechanism. Therefore, we propose a mechanism of Cr(VI)-induced carcinogenesis that involves both genomic instability and epigenetic modification.

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Abbreviations

AC:

Adenocarcinoma

Asc:

Ascorbate

BER:

Base excision repair

CLR:

Crosslink repair

Cr:

Chromium

Cr(III):

Trivalent chromium

Cr(VI):

Hexavalent chromium

DNA:

Deoxyribonucleic acid

DSB:

DNA double-strand break

H3K4me3:

Trimethylated histone 3 at lysine 4

H3K9me2:

Dimethylated histone 3 at lysine 9

HR:

Homologous recombination

IF:

Immunofluorescence

miRNA:

MicroRNA

MMR:

Mismatch repair

NHEJ:

Nonhomologous end joining

NSCC:

Non-small cell carcinoma

SCC:

Small cell carcinoma

SqCC:

Squamous cell carcinoma

WB:

Western blot

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Acknowledgments

This work was supported by the National Institute of Environmental Health Sciences [ES016893 to J.P.W] and the National Aeronautics and Space Administration (NASA) [ACD FSB-2009 to J.P.W].

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, School of Medicine, Wise Laboratory of Environmental and Genetic Toxicology, University of Louisville, 505 S. Hancock St, CTRB Rm 522, Louisville, KY, 40292, USA

    Cynthia L. Browning, Rachel M. Speer & John Pierce Wise Sr.

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  1. Cynthia L. Browning
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  2. Rachel M. Speer
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Correspondence to John Pierce Wise Sr. .

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  1. Natl Ctr Envtl Assessment Office of Res and Devt, Research Triangle Park, North Carolina, USA

    Anuradha Mudipalli

  2. Professor of Environmental Medicine, New York University, Tuxedo, New York, USA

    Judith T. Zelikoff

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Browning, C.L., Speer, R.M., Wise, J.P. (2017). Molecular Mechanisms of Chromium-Induced Carcinogenesis. In: Mudipalli, A., Zelikoff, J. (eds) Essential and Non-essential Metals. Molecular and Integrative Toxicology. Humana Press, Cham. https://doi.org/10.1007/978-3-319-55448-8_7

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