Complexities of chromium carcinogenesis: role of cellular response, repair and recovery mechanisms

doi:10.1016/j.mrfmmm.2003.09.006

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis

Volume 533, Issues 1–2, 10 December 2003, Pages 3-36

https://doi.org/10.1016/j.mrfmmm.2003.09.006 Get rights and content

Abstract

Certain hexavalent chromium (Cr(VI))-containing compounds are recognized occupational human lung carcinogens and may pose an environmental health risk. The carcinogenicity of Cr(VI) is targeted to particulate forms of moderate to low solubility. Soluble Cr(VI) oxyanions in the immediate cellular microenvironment traverse the cell membrane by non-specific anionic transporters. Cr(VI) is reductively metabolized within cells by agents including ascorbic acid (Asc), glutathione (GSH) and cysteine (Cys). During Cr(VI) reduction, a diverse range of genetic lesions are generated including Cr–DNA binary (mono) adducts, Cr–DNA ternary adducts, DNA protein crosslinks (DPCs), bi-functional (DNA interstrand crosslinks (ICLs)) adducts, single-strand breaks (SSBs) and oxidized bases. Some forms of Cr damage, such as ICLs, present physical barriers to DNA replication/transcription and, thus, likely promote a terminal cell fate such as apoptosis or terminal growth arrest. Other lesions, such as ternary DNA adducts, are potentially pre-mutagenic. Cr(VI) exposure elicits a classical DNA damage response within cells including activation of the p53 signaling pathway and cell cycle arrest or apoptosis. Moreover, Cr(VI) also induces the ATM-dependent DNA damage response pathway which is paradoxically required for both apoptosis and survival after Cr(VI) insult. In yeast, moderately cytotoxic concentrations of Cr(VI) result in an initial G1 arrest and delayed S phase progression, whereas less toxic levels of Cr(VI) induce G2 arrest, which requires homologous recombination for exit and survival. The past several years has witnessed many important advances in our understanding of the genetic/cellular damage produced by exposure to Cr(VI). Further information is needed regarding the potential involvement of oxygen radicals in Cr genotoxicity, the specific DNA repair pathways activated by Cr and the complex signaling mechanisms involved in the cellular response to Cr(VI). These pertinent issues must be considered in relation to the potential role that each plays in the induction of human respiratory tract cancer by particulate Cr(VI) compounds.

Section snippets

Chromium: background information

Chromium (Cr) is ubiquitous in the environment, occurring naturally in soils, rocks and living organisms. Cr exists in primarily two valence states, trivalent (Cr(III)) and hexavalent (Cr(VI)), with the latter primarily produced by anthropogenic sources. Cr(III) is a micronutrient important in the biological activity (receptor binding) of insulin [1] and, accordingly can be found in many dietary supplements. Cr(III) and Cr(VI) are produced by many different industries including welding, chrome

General information

Cr in its hexavalent state (Cr(VI)), exhibits very little biological activity (i.e. interaction with cellular macromolecules) at toxicologically relevant concentrations. Under physiological conditions, Cr(VI) exists as a chromate oxyanion and crosses the cell membrane through non-specific phosphate/sulfate anionic transporters [25], [26]. Within the cell, Cr(VI) undergoes rapid metabolic reduction by ascorbic acid (Asc) and low molecular weight thiols including reduced glutathione (GSH) and

General information

Cr(VI)-containing compounds are genotoxic and can induce gene mutations [66], [67], [68], sister chromatid exchanges [69], [70], [71], [72], [73], and chromosomal aberrations [71], [72], [73], [74], [75], [76], [77]. Cr(VI) alone does not react with isolated DNA, as the cellular constituents of reductive metabolism must be present for Cr to damage macromolecules. The ultimate, and most stable, reductive metabolite of Cr(VI) is Cr(III). The trivalent form of Cr is unable to easily pass through

Repair of Cr-induced DNA damage

While the mutational consequences arising from Cr-genotoxicity have been well-studied, very little is known regarding the repair of Cr–DNA damage. This is intriguing considering the potential human health relevance of this metal. Most of the difficulty has been related to the complexity and diversity of Cr-lesions. The extreme reactivity of Cr species (i.e. Cr(III) and Cr(V)) towards both DNA bases and phosphates presents a substantial obstacle in synthesizing site-specific oligonucleotides, a

Cr-induced mutagenesis

The characterization of Cr-induced mutagenic events has been extensively investigated in both bacterial [226], [229] and mammalian systems [66], [67], [68]. Cr(VI) is a reasonably potent mutagen at the hypoxanthine–guanine phosphoribosyl transferase (HGPRT) locus (6-thioguanine resistance) [66], [67], [68], [147], [148], [247], [248], but is unable to induce mutations with the NaK ATPase locus (ouabain resistance) [247], [248]. The former assay detects a broad spectrum of mutations whereas the

Cellular response to Cr(VI) exposure

It is well-established that the mutagenic and transforming actions of Cr(VI) are only observed under treatment regimens which evoke some cellular toxicity. The major cellular targets of Cr(VI) toxicity are lung epithelial cells and fibroblasts that are exposed to relatively high concentrations of soluble Cr(VI) in the immediate microenvironment of inhaled particles [4]. Soluble chromates can be used to study the genotoxic effects of Cr(VI) in cell culture. The uptake of ionic Cr has been

Conclusions and research needs

A tremendous amount of research effort has been dedicated to understanding the human health effects associated with exposure to Cr(VI) and the molecular mechanisms by which they occur. Yet, the research community is still unclear on matters such as the exact role of reactive oxygen species in this process which is complicated by the oxidizing potential of Cr (as Cr(V)) and the propensity to use extraordinarily toxic concentrations for studies of this type. Additionally, while the diverse

Acknowledgements

Because of space limitations the authors apologize for any studies that were not mentioned in this review.

References (330)

R.A. Anderson
Nutritional role of chromium
Sci. Total Environ.
(1981)
V. Bianchi et al.
Review of genetic effects and mechanisms of action of chromium compounds
Sci. Total Environ.
(1988)
S. De Flora et al.
Genotoxicity of chromium compounds. A review
Mutat. Res.
(1990)
E.T. Snow
Metal carcinogenesis: mechanistic implications
Pharmacol. Ther.
(1992)
A. Leonard et al.
Carcinogenicity and mutagenicity of chromium
Mutat. Res.
(1980)
W. Yu et al.
Preconception urethane or chromium(III) treatment of male mice: multiple neoplastic and non-neoplastic changes in offspring
Toxicol. Appl. Pharmacol.
(1999)
R. Cheng et al.
Microarray analysis of altered gene expression in the TM4 sertoli-like cell line exposed to chromium(III) chloride
Reprod. Toxicol.
(2002)
P. Arslan et al.
Intracellular chromium reduction
Biochim. Biophys. Acta
(1987)
A. Mikalsen et al.
Microsomal metabolism of hexavalent chromium. Inhibitory effect of oxygen and involvement of cytochrome P-450
Chem. Biol. Interact.
(1989)
A. Mikalsen et al.
Reduction of hexavalent chromium in a reconstituted system of cytochrome P-450 and cytochrome b5
Chem. Biol. Interact.
(1989)

D. Ryberg et al.

Inhibitory action of hexavalent chromium (Cr(VI)) on the mitochondrial respiration and a possible coupling to the reduction of Cr(VI)

Biochem. Pharmacol.

(1984)

D. Ryberg et al.

Mechanisms of chromium toxicity in mitochondria

Chem. Biol. Interact.

(1990)

X.L. Shi et al.

Chromium(V) and hydroxyl radical formation during the glutathione reductase-catalyzed reduction of chromium(VI)

Biochem. Biophys. Res. Commun.

(1989)

S. Kawanishi et al.

Mechanism of DNA cleavage induced by sodium chromate(VI) in the presence of hydrogen peroxide

J. Biol. Chem.

(1986)

A. Meister

Glutathione-ascorbic acid antioxidant system in animals

J. Biol. Chem.

(1994)

J. Chen et al.

Mutational spectrum of chromium(VI) in human cells

Mutat. Res.

(1994)

V. Bianchi et al.

Genetic effects of chromium compounds

Mutat. Res.

(1983)

M. Sugiyama

Role of physiological antioxidants in chromium(VI)-induced cellular injury

Free Rad. Biol. Med.

(1992)

V. Bianchi et al.

Mechanisms of chromium toxicity in mammalian cell cultures

Toxicology

(1980)

M.J. Tsapakos et al.

The interaction of chromium with nucleic acids

Chem. Biol. Interact.

(1983)

X.L. Shi et al.

Evidence for a Fenton-type mechanism for the generation of OH radicals in the reduction of Cr(VI) in cellular media

Arch. Biochem. Biophys.

(1990)

G. Tamino et al.

Effects of the trivalent and hexavalent chromium on the physicochemical properties of mammalian cell nucleic acids and synthetic polynucleotides

Chem. Biol. Interact.

(1981)

B. Gulanowski et al.

Impact of chromium ions on nucleoside triphosphates and nucleic acids

J. Inorg. Biochem.

(1992)

H. Arakawa et al.

A comparative study of calf thymus DNA binding to Cr(III) and Cr(VI) ions. Evidence for the guanine N-7-chromium-phosphate chelate formation

J. Biol. Chem.

(2000)

M. Casadevall et al.

Chromium(VI)-mediated DNA damage: oxidative pathways resulting in the formation of DNA breaks and abasic sites

Chem. Biol. Interact.

(1999)

J. Singh et al.

Sensitive quantitation of chromium–DNA adducts by inductively coupled plasma mass spectrometry with a direct injection high-efficiency nebulizer

Toxicol. Sci.

(1998)

L. Fishbein

Sources, transport and alteration of metal compunds: an overview. I. Arsenic, beryllium, cadmium, chromium and nickel

Environ. Health Perspect.

(1981)

P.H.S. US Department of Health and Human Services, Agency for Toxic Substances and Disease Registry Toxicological...

IARC Monograph on the Evaluation of Carcinogenic Risk to Humans, Chromium, Nickel and Welding, Lyon, France,...

K. Salnikow et al.

Analysis of the binding sites of chromium to DNA and protein in vitro and in intact cells

Carcinogenesis

(1992)

S. De Flora

Threshold mechanisms and site specificity in chromium(VI) carcinogenesis

Carcinogenesis

(2000)

K.D. Sugden et al.

The role of chromium(V) in the mechanism of chromate-induced oxidative DNA damage and cancer

J. Environ. Pathol. Toxicol. Oncol.

(2000)

J. Singh et al.

Chromium-induced genotoxicity and apoptosis: relationship to chromium carcinogenesis (review)

Oncol. Rep.

(1998)

EPA Health Assessment Document for Chromium, Environmental Assessment and Crtieria Office, US Environmental Protection...

EPA Locating and Estimating Air Emissions from Sources of Chromium, Office of Air Quality Planning and Standards, US...

EPA Health Effects Assessment for Hexavalent Chromium, Office of Emrgency and Remedial Response, US Environmental...

IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, International Agency for Research on...

W. Machle et al.

Cancer of the respiratory system in the United States chromate-producing industry

Publ. Health Rep.

(1948)

L.S. Levy et al.

Investigation of the potential carcinogenicity of a range of chromium containing materials on rat lung

Br. J. Ind. Med.

(1986)

R. Cheng et al.

Increased serum corticosterone and glucose in the offsrping of chromium(III)-treated male mice

Environ. Health Perspect.

(2002)

Y. Ishikawa et al.

Characteristics of chromate workers’ cancers, chromium lung deposition and precancerous bronchial lesions: an autopsy study

Br. J. Cancer

(1994)

Y. Ishikawa et al.

“Hot spots” of chromium accumulation at bifurcations of chromate workers’ bronchi

Cancer Res.

(1994)

P.J. Sheehan et al.

Assessment of the human health risks posed by exposure to chromium-contaminated soils

J. Toxicol. Environ. Health

(1991)

B. Buttner et al.

Modification of the erythrocyte anion carrier by chromate

Xenobiotica

(1985)

A. Mikalsen et al.

Reductive metabolism and protein binding of chromium(VI) by P450 protein enzymes

Carcinogenesis

(1991)

R.B. Banks et al.

Chromate reduction by rabbit liver aldehyde oxidase

Biochem. Biophys. Res. Commun.

(1986)

D.I. Pattison et al.

Chromium(VI) reduction by catechol(amine)s results in DNA cleavage in vitro: relevance to chromium genotoxicity

Chem. Res. Toxicol.

(2001)

S. DeFlora et al.

Pominent role of DT-diaphorase as a cellular mechanim reducing chromium(VI) and reverting its mutagenicity

Cancer Res.

(1985)

S. De Flora et al.

Estimates of the chromium(VI) reducing capacity in human body compartments as a mechanism for attenuating its potential toxicity and carcinogenicity

Carcinogenesis

(1997)

G. Quievryn et al.

Genotoxicity and mutagenicity of chromium(VI)/ascorbate-generated DNA adducts in human and bacterial cells

Biochemistry

(2003)

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ReviewComplexities of chromium carcinogenesis: role of cellular response, repair and recovery mechanisms

Abstract

Section snippets

Chromium: background information

General information

General information

Repair of Cr-induced DNA damage

Cr-induced mutagenesis

Cellular response to Cr(VI) exposure

Conclusions and research needs

Acknowledgements

Sci. Total Environ.

Sci. Total Environ.

Mutat. Res.

Pharmacol. Ther.

Mutat. Res.

Toxicol. Appl. Pharmacol.

Reprod. Toxicol.

Biochim. Biophys. Acta

Chem. Biol. Interact.

Chem. Biol. Interact.

Biochem. Pharmacol.

Chem. Biol. Interact.

Biochem. Biophys. Res. Commun.

J. Biol. Chem.

J. Biol. Chem.

Mutat. Res.

Mutat. Res.

Free Rad. Biol. Med.

Toxicology

Chem. Biol. Interact.

Arch. Biochem. Biophys.

Chem. Biol. Interact.

J. Inorg. Biochem.

J. Biol. Chem.

Chem. Biol. Interact.

Toxicol. Sci.

Sources, transport and alteration of metal compunds: an overview. I. Arsenic, beryllium, cadmium, chromium and nickel

Environ. Health Perspect.

Analysis of the binding sites of chromium to DNA and protein in vitro and in intact cells

Carcinogenesis

Threshold mechanisms and site specificity in chromium(VI) carcinogenesis

Carcinogenesis

The role of chromium(V) in the mechanism of chromate-induced oxidative DNA damage and cancer

J. Environ. Pathol. Toxicol. Oncol.

Chromium-induced genotoxicity and apoptosis: relationship to chromium carcinogenesis (review)

Oncol. Rep.

Cancer of the respiratory system in the United States chromate-producing industry

Publ. Health Rep.

Investigation of the potential carcinogenicity of a range of chromium containing materials on rat lung

Br. J. Ind. Med.

Increased serum corticosterone and glucose in the offsrping of chromium(III)-treated male mice

Environ. Health Perspect.

Characteristics of chromate workers’ cancers, chromium lung deposition and precancerous bronchial lesions: an autopsy study

Br. J. Cancer

“Hot spots” of chromium accumulation at bifurcations of chromate workers’ bronchi

Cancer Res.

Assessment of the human health risks posed by exposure to chromium-contaminated soils

J. Toxicol. Environ. Health

Modification of the erythrocyte anion carrier by chromate

Xenobiotica

Reductive metabolism and protein binding of chromium(VI) by P450 protein enzymes

Carcinogenesis

Chromate reduction by rabbit liver aldehyde oxidase

Biochem. Biophys. Res. Commun.

Chromium(VI) reduction by catechol(amine)s results in DNA cleavage in vitro: relevance to chromium genotoxicity

Chem. Res. Toxicol.

Pominent role of DT-diaphorase as a cellular mechanim reducing chromium(VI) and reverting its mutagenicity

Cancer Res.

Estimates of the chromium(VI) reducing capacity in human body compartments as a mechanism for attenuating its potential toxicity and carcinogenicity

Carcinogenesis

Genotoxicity and mutagenicity of chromium(VI)/ascorbate-generated DNA adducts in human and bacterial cells

Biochemistry

Review
Complexities of chromium carcinogenesis: role of cellular response, repair and recovery mechanisms