Cadmium is a non-physiological heavy metal released into the environment and workplace as a result of industrial, municipal, and agricultural activities. Cadmium has been shown to be a pulmonary, prostatic, and testicular carcinogen in animals and humans. While the incidence of cancer via cadmium intoxication continues to grow at an alarming rate, the underlying molecular mechanisms of CD-induced carcinogenicity remain largely elusive. The long-range objective of this study is to understand of this study to under the molecular mechanisms of Cd intoxication. This will be achieved through the following specific aims: (a) to investigate zinc replacement by Cd in Zn-dependent enzymes, (b) to investigate the molecular role of reactive oxygen species in DNA strand damage, and (c) to investigate Cd-induced intracellular redox changes as reflected by decreases in the activities/levels of antioxidant enzymes and certain metabolites and correlate these losses to Cd-induced DNA strand breaks (Comet assay). In vitro and in vivo studies using selected Zn-dependent enzymes will be carried out to replace Zn with Cd and correlate the effects of this replacement to quantifiable DNA damage. Direct free radical attack of DNA will be studied by isolating and identifying oxidation products using gas chromatography-ion monitoring-mass spectrometry. The free radical- induced oxidative DNA damage products yields will be correlated to DNA strand breaks quantifiable by the single cell gel electrophoresis or Comet assay. Data from these studies will shed light on the molecular lesions of Cd intoxication.
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