UICC World Cancer Congress 2006

Objective:Collective assessment of trace element profile at cellular and sub-cellular levels is gaining importance today because elemental ratios are shown to be diagnostic and prognostic markers for health evaluation. Available reports document alterations in elements associated with different diseases, even neoplastic development. Though it has been postulated that accumulation of iron can trigger pre-neoplastic foci, its exact role in carcinogenic process is unknown. Our study is an attempt to investigate status of iron in association with other biologically important metal ions, free radical generation process and antioxidant profile during pre-initiation stage of induced hepatocarcinogenesis.

Methods:Swiss albino mice administered with dietary p-dimethylaminoazobenzine(p-DAB) for five weeks were assessed for elemental profile and oxidant-antioxidant status. Energy-dispersive-X-ray-fluorescence(EDXRF) spectrometer was employed for the assessment of trace elements in lyophilized powdered liver samples. Assessment of intracellular oxidative stress was done microscopically and by luminescence spectrometer using dihydrorhodamine 123 in whole blood. Activity of antioxidant enzymes, superoxide dismutase(SOD), and catalase(CAT) were determined spectrophotometrically.

Results:Remarkable increase (>3-10 folds) in iron level noted in a time-dependant manner in liver and also its sub-cellular organelles of the p-DAB administered animals show possible association of iron overload with carcinogenic progression. Similar trend was observed for nickel only in the whole liver (~6 fold). Results show depletion in selenium level in both nucleus and mitochondria and depletion of Cu only in mitochondria. The observed enhancement of ROS production complies with the noted alterations in SOD and CAT. Data suggest intricate balance of specific elements involved in tuning of the molecular network of metabolic pathways.