Cadmium (Cd) is a ubiquitous environmental pollutant of increasing
worldwide concern. It is thought to be of greater concern to rapidly
industrializing developing countries because of the increasing pace of
industrial activities in these countries with increasing consumption
and release into the environment. Traditionally, health concerns in
exposed human populations have revolved around the association of Cd
with bone disease, emphysema and possibly hypertension. Accumulating
evidence suggest that Cd is involved in the disruption of many genomic
processes, the mechanisms of which are being gradually understood.
Changes in DNA Methylation may be induced by cadmium leading to
epigenetic alterations. Additionally, though Cd is not thought to
induce reactive oxygen species (ROS) directly because it is not capable
of accepting or donating electrons under physiological conditions,
8-hydroxy deoxyguanosine (8-OHdG) (a marker of oxidative stress to DNA
and a risk factor for cancer among others) has been shown to be
elevated in the DNA of testes from rats treated with cadmium chloride,
at least in part because Cd inhibits DNA repair mechanisms. Cadmium is
also a metabolic antagonist to Zinc (Zn), an important micronutrient
involved in numerous molecular activities. This antagonism alters the
physiological stoichiometric relationship between Cd and Zn leading to
high Cd/Zn ratio, one consequence of which is high error rate and lack
of efficient DNA repair systems leading to high mutation and genome
instability culminating in many carcinogenic states, particularly
prostate carcinogenesis. Cadmium has also been shown to replace Zn in
the tumor suppressor protein, p53 thereby impairing p53's DNA binding
activity and associated repair processes. The expression of the p53
protein is significantly depressed by cadmium. Although the rising
level of Cd in the environment is widely acknowledged, the occult
threat it poses to genome stability largely through inhibition of
normal DNA damage repair, oxidative stress and apoptosis and health is
poorly recognized. This paper examines the involvement of Cd in the
molecular pathways of human disease, providing insight for the
prevention of genome instability and associated disease susceptibility
particularly cancer across populations through micronutrient
intervention, aiding upregulation of the antioxidant defense and DNA
repair systems