The effect of vitamin A deficiency on the initiation and postinitiation phases of benzo(a)pyrene-induced lung tumourigenesis in rats

Dogra, Sunil; Khanduja, Krishan Lal; Gupta, Mahesh P.

doi:10.1038/bjc.1985.279

Cited by 20 publications

(4 citation statements)

References 12 publications

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“…Subsequent studies have demonstrated enhanced lung carcinogenesis in vitamin A-deficient animals exposed to the tobacco carcinogen benzo[a]pyrene, possibly due to enhanced binding of the carcinogen to tracheal epithelial DNA. 2,3 These findings have paved the way to vitamin A intervention in experimental lung carcinogenesis. 4,5 The extension of these studies to human lung carcinogenesis and prevention was supported by epidemiologic studies, which suggested that significant dietary intake of vitamin A and carotenoids plays an important role in decreased cancer incidence.…”

Section: An Initial Era Of Optimismmentioning

confidence: 94%

Retinoids in Lung Cancer: Friend, Foe, or Fellow Traveler?

Khuri

Lotan

2004

JCO

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Section: An Initial Era Of Optimismmentioning

confidence: 94%

Retinoids in Lung Cancer: Friend, Foe, or Fellow Traveler?

Khuri

Lotan

2004

JCO

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“…Vitamin A deficiency has been reported to cause preneoplastic changes in tracheal [ 3 ] and bronchial epithelium and to be associated with an increased risk of lung cancer [ 4 , 5 ]. The loss of retinoic acid receptor beta (RARβ), one of the vitamin A nuclear receptors, is partly responsible for the lung carcinogenesis in vitamin A deficient individuals [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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BackgroundWe 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.ResultsWe 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 γ 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.ConclusionsFindings 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.

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“…Subsequent epidemiological, preclinical and clinical studies established a relationship between vitamin A deficiency and a higher incidence of carcinogenesis in both humans and rodents (Basu, Temple, & Hodgson, 1988; Chaudhy, Jafarey, & Ibrahim, 1980; S. C. Dogra, Khanduja, & Gupta, 1985; Ito, Gajalakshmi, Sasaki, Suzuki, & Shanta, 1999; Stehr, Gloninger, Kuller, Marsh, Radford, & Weinberg, 1985).…”

Section: Cyp26 and Retinoic Acid In Cancermentioning

confidence: 99%

Role of Retinoic Acid-Metabolizing Cytochrome P450s, CYP26, in Inflammation and Cancer

Stevison

Jing

Tripathy

et al. 2015

Advances in Pharmacology

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Vitamin A (retinol) and its active metabolite, all-trans-retinoic acid (atRA), play critical roles in regulating the differentiation, growth and migration of immune cells. Similarly, as critical signaling molecules in the regulation of the cell cycle, retinoids are important in cancers. Concentrations of atRA are tightly regulated in tissues, predominantly by the availability of retinol, synthesis of atRA by ALDH1A enzymes and metabolism and clearance of atRA by CYP26 enzymes. The ALDH1A and CYP26 enzymes are expressed in several cell types in the immune system and in cancer cells. In the immune system the ALDH1A and CYP26 enzymes appear to modulate RA concentrations. Consequently, alterations in the activity of ALDH1A and CYP26 enzymes are expected to change disease outcomes in inflammation. There is increasing evidence from various disease models of intestinal and skin inflammation that treatment with atRA has a positive effect on disease markers. However, whether aberrant atRA concentrations or atRA synthesis and metabolism play a role in inflammatory disease development and progression is not well understood. In cancers, especially in acute promyelocytic leukemia and neuroblastoma, increasing intracellular concentrations of atRA appears to provide clinical benefit. Inhibition of the CYP26 enzymes to increase atRA concentrations and combat therapy resistance has been pursued as a drug target in these cancers. This chapter covers the current knowledge of how atRA and retinol regulate the immune system and inflammation, how retinol and atRA metabolism is altered in inflammation and cancer and what roles atRA metabolizing enzymes have in immune responses and cancers.

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The effect of vitamin A deficiency on the initiation and postinitiation phases of benzo(a)pyrene-induced lung tumourigenesis in rats

Cited by 20 publications

References 12 publications

Retinoids in Lung Cancer: Friend, Foe, or Fellow Traveler?

Retinoids in Lung Cancer: Friend, Foe, or Fellow Traveler?

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

Role of Retinoic Acid-Metabolizing Cytochrome P450s, CYP26, in Inflammation and Cancer

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