Selenium is an essential nutrient with multiple physiological actions, and has a major role in the functioning of several important proteins. Consumption of selenium higher than Recommended Dietary Allowance (RDA) is suggested to protect against some cancers. The causal association between the highly persistent environmental pollutants, polychlorinated biphenyls (PCBs) and human cancer risk has been debated for some time. PCBs are known tumor promoters and have been found to be carcinogenic in rodent models. In order to assess the effect of selenium on a PCB-exposed population, blood samples were collected from 103 Inuit from Salluit, a village in Northern Canada. The subjects were 22-70 years old and comprised of 33 males and 70 females. The Inuit traditional diet includes blubber from sea mammals and fatty fish which accumulate non-biodegradable PCBs. Because of the nature of the diet, the Inuit also had a significant intake of selenium, a known antioxidant. Blood selenium was analyzed by inductively coupled plasma/mass spectrometry after nitric acid digestion. The levels were in the range of 227 to 2,069 µg/L. Plasma PCB levels were determined by high-resolution gas chromatography with electron-capture detection and found to be in the range of 1.7 to 143 µg/L. DNA isolated from the WBCs were analyzed by modified 32P-postlabeling adductomics technology. This assay which involves enzymatic digestion of DNA, adduct enrichment, 32P-labeling and PEI-cellulose TLC in solvents with increasing salt concentrations, showed a multitude of highly polar to highly lipophilic adducts. The adduct patterns obtained within the WBC samples were comparable; however, a large inter-individual variability was observed. The levels of 8-oxodG, identified as the benchmark oxidative DNA lesion, ranged from 470 to 7,400 adduct/109 nucleotides. Other polar adducts showed a 30 to 800-fold inter-individual variability. The most lipophilic adducts of the Diagonal Radioactive Zone (DRZ) were below the detection limit. The subjects were classified into two groups, high and low, with high group consisting of those with a molar ratio of selenium/PCB of 40 or more. When restricted to the high selenium/PCB group, selenium was found to be significantly negatively correlated with the levels of 8-oxodG (r = -0.58, p-value = 0.0004) and total adducts (r = -0.53, p-value = 0.0014) while there was no significant correlation with either adducts within the low selenium/PCB group. This study suggests increasing selenium levels to counter the effect of PCBs thereby reducing the damage to DNA (Supported by ES 07380).

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA