Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

Molecular and cellular mechanisms of cadmium carcinogenesis.

Authors
Waisberg-M; Joseph-P; Hale-B; Beyersmann-D
Source
Toxicology 2003 Nov; 192(2-3):95-117
NIOSHTIC No.
20032132
Abstract
Cadmium is a heavy metal, which is widely used in industry, affecting human health through occupational and environmental exposure. In mammals, it exerts multiple toxic effects and has been classified as a human carcinogen by the International Agency for Research on Cancer. Cadmium affects cell proliferation, differentiation, apoptosis and other cellular activities. Cd2+ does not catalyze Fenton-type reactions because it does not accept or donate electrons under physiological conditions, and it is only weakly genotoxic. Hence, indirect mechanisms are implicated in the carcinogenicity of cadmium. In this review multiple mechanisms are discussed, such as modulation of gene expression and signal transduction, interference with enzymes of the cellular antioxidant system and generation of reactive oxygen species (ROS), inhibition of DNA repair and DNA methylation, role in apoptosis and disruption of E-cadherin-mediated cell-cell adhesion. Cadmium affects both gene transcription and translation. The major mechanisms of gene induction by cadmium known so far are modulation of cellular signal transduction pathways by enhancement of protein phosphorylation and activation of transcription and translation factors. Cadmium interferes with antioxidant defense mechanisms and stimulates the production of reactive oxygen species, which may act as signaling molecules in the induction of gene expression and apoptosis. The inhibition of DNA repair processes by cadmium represents a mechanism by which cadmium enhances the genotoxicity of other agents and may contribute to the tumor initiation by this metal. The disruption of E-cadherin-mediated cell-cell adhesion by cadmium probably further stimulates the development of tumors. It becomes clear that there exist multiple mechanisms which contribute to the carcinogenicity of cadmium, although the relative weights of these contributions are difficult to estimate.
Keywords
Cadmium-compounds; Cancer; Carcinogenesis; Oxidative-processes; DNA-damage; Gene-mutation; Genes; Cell-function; Toxic-effects; Heavy-metals; Enzyme-activity; Enzymes; Antioxidants; Tumors; Cell-differentiation; Cellular-reactions; Genotoxicity; Proteins
Contact
Department of Land Resource Science, University of Guelph, Guelph, Ontario, Canada
CODEN
TXCYAC
CAS No.
7440-43-9; 70-18-8
Publication Date
20031105
Document Type
Journal Article
Email Address
mwaisberg@ig.com.br
Fiscal Year
2004
NTIS Accession No.
NTIS Price
Issue of Publication
2-3
ISSN
0300-483X
NIOSH Division
HELD
Source Name
Toxicology
State
WV
TOP