Molecular mechanisms of cadmium induced mutagenicity

Abstract

<jats:p> Cadmium is a human carcinogen of worldwide concern because it accumulates in the environment due to its extremely long half-life. Its compounds are classified as human carcinogens by several regulatory agencies. Cadmium affects cell proliferation, differentiation, apoptosis and other cellular activities and can cause numerous molecular lesions that would be relevant to carcinogenesis. For a long time cadmium has been considered as a non-genotoxic carcinogen, as it is only weakly mutagenic in bacterial and mammalian cell test systems. Recently, we presented evidence that when assayed in a test system, in which both intragenic and multilocus mutations can be detected, cadmium acts as a strong mutagen which induces predominantly multilocus deletions. In this review, we discuss two mechanisms that play an important role in cadmium mutagenicity: (i) induction of reactive oxygen species (ROS); and (ii) inhibition of DNA repair. Experimental evidence suggests that cadmium at low, for environmental exposure relevant concentrations, induces mutations by inducing oxidative DNA damage and that it decreases genetic stability by inhibiting the repair of endogenous and exogenous DNA lesions, which in turn increase the probability of mutations and consequently cancer initiation by this metal. </jats:p>

Chronic exposure to low concentrations of waterborne cadmium during embryonic and larval development results in the long‐term hindrance of antipredator behavior in zebrafish

“…Cadmium is a widespread pollutant in aquatic environments worldwide; it has been shown to be toxic at very low concentrations and is a known carcinogen, mutagen, and immunotoxin [1][2][3][4][5]. The possible danger of increasing metal concentrations in the environment is overshadowed by the fact that documented cases of metal-induced mortality at environmentally relevant concentrations are extremely rare [6].…”

Protective effects of Selenium and/or Melatonin against Cadmium Chloride induced Chromosomal aberrations in Swiss Albino mice Mus musculus BALB/c

“…Cadmium also induces cell proliferation, inactivates negative growth stimuli, such as the tumor suppressor protein p53. (Filipic et al, 2006;Hartwig, 2010). It has been suggested that cadmium can cause aneuploidy, and it poisons the mitotic spindle.…”

Assessment of Beneficial Effect of Propolis against Cadmium Induced Toxicity and Oxidative Stress in Rats.

“…Similar results showed by many previous study [76][77][78][79][80][81] . Cd generate free radicals and ROS such as H2O2, superoxide O2( -) and hydroxyl radical (OH -), nitric oxide (NO -)3 and can reduce the level of the main antioxidant compounds in the cells by inactivating enzymes and other antioxidant molecules 82 . As a result, lipid peroxidation is generated.…”