Recently published reports provide evidence that supplemental selenium can substantially reduce the incidence and mortality of several types of cancer, including lung cancer. To further investigate these provocative findings, we propose a randomized, placebo-controlled, double-blind chemopreventive trial with 150 participants (75 subjects per arm) using a placebo tablet or a tablet containing 200mug high-selenium brewer's yeast per day, given for duration of six months. Blood, urine, and sputum specimen will be collected at baseline, and after 3 and 6 months of intervention.
Our specific aims are stated in the following questions. 1) does selenium supplementation decrease the frequency of cellular atypia detected in sputum ? Sputum atypia is an established risk factor for lung cancer and has been documented to occur in approximately 80 percent of our cohort. We will determine if supplementation with selenium decrease the incidence sensitivity to detect changes mediated by selenium may be limited using cellular atypia as endpoint, we will also determine if selenium induces changes in lung epithelial cell nuclear morphometry which are reflective of changes in lung cancer risk. 2) Does selenium supplementation decrease indicators of oxidative cellular damage in either blood, urine or the lung ? Chronic inflammation has been implicated as one outcome attribute to asbestos exposure. Given the well known involvement of selenium in number of selenoproteins, some of which protect cells against oxidative damage, this population of asbestos-exposed individuals present an idea cohort in which directly assess whether selenium decrease oxidative damage to cellular marcomolecules in individuals that are oxidatively challenged, and that may have higher nutritional requirements for antioxidant defense due to oxidative stress. To evaluate this question, we will measure several indices of oxidative damage reported to be elevated in asbestos-exposed individuals. These markers include 8-hydroxydeoxyguanosine (8-OhdG), malondialdehyde(MDA) and 8-isoprostaglandin F2 - alpha (8-EPG) in plasma and urine. Levels of these indices will be determined at baseline and after 3 and 6 months of the selenium supplementation. In addition we will determine the degree of cellular DNA damage in pulmonary epithelial cells from endobronchial biopsy and sputum using the COMET assay (in the presence and absence damage to purines and pyrimidines. Level of MDA and 8-EPG in sputum also will determined. The project proposed will contribute to understanding whether intermediate biomarkers for lung cancer can be reserved by selenium, a finding of potential public health importance.
|Gottschall, E Brigitte; McGinley, John N; Spoelstra, Nicole et al. (2005) Effect of cytological fixative and environmental conditions on nuclear morphometric characteristics of squamous epithelial cells in sputum. Cytometry B Clin Cytom 67:19-26|
|Gottschall, E Brigitte; Wolfe, Pam; Haegele, Albert D et al. (2004) Increased urinary 8-isoprostaglandin F(2)alpha is associated with lower plasma selenium levels and lower vegetable and fruit intake in an asbestos-exposed cohort at risk for lung cancer. Chest 125:83S|