Vitamin A depletion induced by cigarette smoke is associated with an increase in lung cancer-related markers in rats

Background: we have previously demonstrated that cigarette smoke is associated with a significant reduction of retinoic acid in rat lungs and the formation of tracheal precancerous lesions. however,the underlying mechanism of cancer risk induced by vitamin a deficiency is unclear. the purpose of this study was to determine whether the cigarette smoke-induced depletion of vitamin a is related to changes in lung cancer risk-related molecular markers. results: we investigated the roles of the retinoic acid receptors (rars) as well as other biomarkers for potential cancer risk in the lungs of rats exposed to cigarette smoke. twenty-four male weanling rats were fed a purified diet and divided equally into four groups. three experimental groups were exposed to increasing doses of cigarette smoke from 20,40 or 60 commercial cigarettes/day for 5 days/week. after 6 weeks,the retinoic acid concentrations in the lung tissue as measured via high performance liquid chromatography (hplc) significantly decreased (p < 0.01) in cigarette smoke exposed groups. western blot analysis revealed that cigarette smoke exposure increased lung protein expression of rar α in a threshold manner and decreased rar β and rar α expression in a dose-dependent fashion. protein expressions of cyclin e and proliferating cell nuclear antigen (pcna) were increased significantly in a dose-dependent manner in cigarette smoke exposed-groups. additionally,there was a significant increase in protein expression of cjun and cyclin d1 demonstrating a threshold effect similar to that exhibited by rarα,suggesting a potential independent signaling pathway for rarα in lung carcinogenesis. conclusions: findings from this study suggest that cigarette smoke-induced lung retinoic acid depletion may involve two independent pathways,rarα- and rarβ-mediated,responsible for the increased cancer risk associated with cigarette smoke-induced vitamin a deficiency. © 2015 xue et al.