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Cadmium and Cancer

  • Andrea HartwigEmail author
Part of the Metal Ions in Life Sciences book series (MILS, volume 11)

Abstract

Cadmium is an established human and animal carcinogen. Most evidence is available for elevated risk for lung cancer after occupational exposure; however, associations between cadmium exposure and tumors at other locations including kidney, breast, and prostate may be relevant as well. Furthermore, enhanced cancer risk may not be restricted to comparatively high occupational exposure, but may also occur via environmental exposure, for example in areas in close proximity to zinc smelters. The underlying mechanisms are still a matter of manifold research activities. While direct interactions with DNA appear to be of minor importance, elevated levels of reactive oxygen species (ROS) have been detected in diverse experimental systems, presumably due to an inactivation of detoxifying enzymes. Also, the interference with proteins involved in the cellular response to DNA damage, the deregulation of cell growth as well as resistance to apoptosis appears to be involved in cadmium-induced carcinogenicity. Within this context, cadmium has been shown to disturb nucleotide excision repair, base excision repair, and mismatch repair. Particularly sensitive targets appear to be proteins with zinc-binding structures, present in DNA repair proteins such as XPA, PARP-1 as well as in the tumor suppressor protein p53. Whether or not these interactions are due to displacement of zinc or due to reactions with thiol groups involved in zinc complexation or in other critical positions under realistic exposure conditions remains to be elucidated. Further potential mechanisms relate to the interference with cellular redox regulation, either by enhanced generation of ROS or by reaction with thiol groups involved in the regulation of signaling pathways. Particularly the combination of these multiple mechanisms may give rise to a high degree of genomic instability evident in cadmium-adapted cells, relevant not only for tumor initiation, but also for later steps in tumor development.

Keywords

cadmium carcinogenicity DNA damage response genomic instability genotoxicity redox regulation signal transduction zinc 

Abbreviations and Definitions

BER

base excision repair

Bw

body weight

cAMP

cyclic adenosine 3’,5’-monophosphate

EFSA

European Food Safety Authority

FAO

Food and Agriculture Organization of the United Nations

Fpg

formamidopyrimidine DNA glycosylase

GG-NER

global genome nucleotide excision repair

GSH

glutathione

IARC

International Agency for Research on Cancer

JEM

job-exposure-matrix

JNK

c-jun-N-terminal kinase

MAK Commission

(= maximale Arbeitsplatzkonzentration) German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area

MAPK

mitogen activated protein kinases

MMR

mismatch repair

MT

metallothionein

NER

nucleotide excision repair

NF-κB

nuclear factor κB

Nrf2

NF-E2-related factor

Ogg1

8-oxoguanine DNA glycosylase 1

PARP

poly(ADP-ribose) polymerase

PTWI

provisional tolerable weekly intake

ROS

reactive oxygen species

TC-NER

transcription-coupled nucleotide excision repair

TWI

tolerable weekly intake

UVC

ultraviolet C light (the full range is 100–280 nm; but usually in biological experiments 254 nm is applied)

WHO

World Health Organization

XP

xeroderma pigmentosum

XPA

xeroderma pigmentosum group A protein

8-oxoG

8-oxoguanine

8-oxo-dGTPase

8-oxo-dG 5’-triphosphate pyrophosphohydrolase

Notes

Acknowledgments

The author would like to thank Dr. Gunnar Jahnke for critical reading of the manuscript. Research conducted in the author’s laboratory was supported by the Deutsche Forschungsgemeinschaft and by BWPLUS.

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© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Food Chemistry and ToxicologyKarlsruhe Institute of Technology (KIT)KarlsruheGermany

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