Workers exposed to asbestos and cigarettes have a markedly increased risk of developing lung cancer and parenchymal fibrosis. Airway metaplasia and inflammation on bronchoalveolar lavage (BAL) are considered potential early markers for these diseases. Our prior studies have shown an high incidence of both of these lesions in asbestos-exposed workers. Epidemiologic and experimental studies have shown that dietary vitamin A (retinol and beta- carotene) has significant anti-cancer and immunomodulatory effects. However, whether intervention with vitamin A can reduce the mortality or morbidity from either disease and athe mechanisms involved are unknown. Asbestos-exposed workers thus serve as an excellent population to test our hypotheses that: 1) The vitamin A intervention will reduce both bronchial metaplasia and lung inflammation, 2) The mechanism of this effect is through modulation of relevant pulmonary cytokines and 3) Local lung rather than serum retinol levels may be a key modifiable biomarker of susceptibility to lung cancer and/or asbestosis. To test these hypotheses we propose to; 1) Determine the effect of dietary vitamin A on bronchial metaplasia and lung inflammation, 2) Investigate the possible mechanisms involved by determining the expression of relevant lung cytokines, growth factors and oncogene proteins, and 3) Determine whether BAL retinoid and carotenoid levels correlate with early markers of disease and can be modified by the intervention. Identifying early markers of disease and markers of host susceptibility should greatly facilitate such occupational studies. The general approach will be a double-blind placebo controlled 6 month trial of combination beta-carotene and retinol given to 50 asbestos workers. The subjects will be studied before and after the vitamin A intervention with BAL and bronchial biopsies. The proposed studies should provide valuable data on early markers of these occupational diseases, whether vitamin A can modify such biomarkers, the mechanisms involved, and the role of local vitamin A stores. The findings may lead to effective preventive strategies for occupational lung cancer and asbestosis.
| Redlich, C A; Chung, J S; Cullen, M R et al. (1999) Effect of long-term beta-carotene and vitamin A on serum cholesterol and triglyceride levels among participants in the Carotene and Retinol Efficacy Trial (CARET) Atherosclerosis 145:425-32 |
| Redlich, C A; Chung, J S; Cullen, M R et al. (1999) Effect of long-term beta-carotene and vitamin A on serum cholesterol and triglyceride levels among participants in the Carotene and Retinol Efficacy Trial (CARET) Atherosclerosis 143:427-34 |
| Redlich, C A; Blaner, W S; Van Bennekum, A M et al. (1998) Effect of supplementation with beta-carotene and vitamin A on lung nutrient levels. Cancer Epidemiol Biomarkers Prev 7:211-4 |
