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

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dc.contributor.author Xue, Y.
dc.contributor.author Harris, E.
dc.contributor.author Wang, Weiqun
dc.contributor.author Baybutt, R. C.
dc.date.accessioned 2016-04-06T14:51:30Z
dc.date.available 2016-04-06T14:51:30Z
dc.date.issued 2015-10-14
dc.identifier.uri http://hdl.handle.net/2097/32329
dc.description Citation: Xue, Y., Harris, E., Wang, W. Q., & Baybutt, R. C. (2015). Vitamin A depletion induced by cigarette smoke is associated with an increase in lung cancer-related markers in rats. Journal of Biomedical Science, 22, 9. doi:10.1186/s12929-015-0189-0
dc.description 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 alpha in a threshold manner and decreased RAR beta and RAR gamma 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 RAR alpha, suggesting a potential independent signaling pathway for RAR alpha in lung carcinogenesis. Conclusions: Findings from this study suggest that cigarette smoke-induced lung retinoic acid depletion may involve two independent pathways, RAR alpha- and RAR beta-mediated, responsible for the increased cancer risk associated with cigarette smoke-induced vitamin A deficiency.
dc.relation.uri https://doi.org/10.1186/s12929-015-0189-0
dc.rights Attribution 4.0 International (CC BY 4.0)
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject Carcinogenesis
dc.subject Rar Alpha
dc.subject Rar Beta
dc.subject Cjun
dc.subject Pcna
dc.subject Cyclin
dc.title Vitamin A depletion induced by cigarette smoke is associated with an increase in lung cancer-related markers in rats
dc.type Text
dc.date.published 2015
dc.citation.doi 10.1186/s12929-015-0189-0
dc.citation.issn 1021-7770
dc.citation.jtitle Journal of Biomedical Science
dc.citation.spage 9
dc.citation.volume 22
dc.contributor.authoreid wwang
dc.description.version Article: Version of Record


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Attribution 4.0 International (CC BY 4.0) Except where otherwise noted, the use of this item is bound by the following: Attribution 4.0 International (CC BY 4.0)

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