Induction of preneoplastic lung lesions in guinea pigs by cigarette smoke inhalation and their exacerbation by high dietary levels of vitamins C and E

Emerich S. Fiala, Ock Soon Sohn, Chung Xiou Wang, Eleanore Seibert, Junji Tsurutani, Phillip A. Dennis, Karam El-Bayoumy, Rama S. Sodum, Dhimant Desai, Joel Reinhardt, Cesar Aliaga

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The development of effective chemopreventive agents against cigarette smoke-induced lung cancer could be greatly facilitated by the availability of suitable laboratory animal models. Here we report that male Hartley guinea pigs treated with cigarette smoke by inhalation twice a day for 28 days developed preneoplastic lung lesions, including bronchial hyperplasia, dysplasia and squamous metaplasia, analogous to those found in human smokers. The lesions were accompanied by increased expression of proliferating cell nuclear antigen and activation of the serine/threonine kinase Akt in the bronchial epithelium. In contrast, no lung lesions were found in guinea pigs ('sham smoked') that were submitted to identical procedures but without cigarettes. Compared with a diet low in vitamin C (50 p.p.m.) and vitamin E (15 p.p.m.), a diet high in vitamin C (4000 p.p.m.) and vitamin E (40 p.p.m.) significantly increased the incidence of these lesions. The inclusion of 1,4-phenylenebis(methylene)selenocyanate (p-XSC), a synthetic chemopreventive organoselenium compound, in the high vitamin C-high vitamin E diet at a level of 15 p.p.m. as selenium appeared to decrease the lesion incidence. Administration of (-)-epigallocatechin gallate, a powerful green tea polyphenolic antioxidant, at 560 p.p.m. in the drinking water had no effect. As in human smokers, levels of ascorbate in blood plasma, lung, liver and the adrenal glands were significantly decreased by cigarette smoke inhalation. These results identify a relevant in vivo laboratory model of cigarette smoke-induced lung cancer, suggest that p-XSC may have activity as a chemopreventive agent against cigarette smoke-induced lung lesions and provide additional evidence that very high dietary levels of certain antioxidants can have co-carcinogenic activity in cigarette smoke-induced lung cancer.

Original languageEnglish (US)
Pages (from-to)605-612
Number of pages8
JournalCarcinogenesis
Volume26
Issue number3
DOIs
StatePublished - Sep 6 2005

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Vitamin E
Smoke
Tobacco Products
Inhalation
Ascorbic Acid
Guinea Pigs
Lung
Lung Neoplasms
Diet
Organoselenium Compounds
Antioxidants
Protein-Serine-Threonine Kinases
Incidence
Proliferating Cell Nuclear Antigen
Metaplasia
Tea
Adrenal Glands
Selenium
Drinking Water
Hyperplasia

All Science Journal Classification (ASJC) codes

  • Cancer Research

Cite this

Fiala, Emerich S. ; Sohn, Ock Soon ; Wang, Chung Xiou ; Seibert, Eleanore ; Tsurutani, Junji ; Dennis, Phillip A. ; El-Bayoumy, Karam ; Sodum, Rama S. ; Desai, Dhimant ; Reinhardt, Joel ; Aliaga, Cesar. / Induction of preneoplastic lung lesions in guinea pigs by cigarette smoke inhalation and their exacerbation by high dietary levels of vitamins C and E. In: Carcinogenesis. 2005 ; Vol. 26, No. 3. pp. 605-612.
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Induction of preneoplastic lung lesions in guinea pigs by cigarette smoke inhalation and their exacerbation by high dietary levels of vitamins C and E. / Fiala, Emerich S.; Sohn, Ock Soon; Wang, Chung Xiou; Seibert, Eleanore; Tsurutani, Junji; Dennis, Phillip A.; El-Bayoumy, Karam; Sodum, Rama S.; Desai, Dhimant; Reinhardt, Joel; Aliaga, Cesar.

In: Carcinogenesis, Vol. 26, No. 3, 06.09.2005, p. 605-612.

Research output: Contribution to journalArticle

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T1 - Induction of preneoplastic lung lesions in guinea pigs by cigarette smoke inhalation and their exacerbation by high dietary levels of vitamins C and E

AU - Fiala, Emerich S.

AU - Sohn, Ock Soon

AU - Wang, Chung Xiou

AU - Seibert, Eleanore

AU - Tsurutani, Junji

AU - Dennis, Phillip A.

AU - El-Bayoumy, Karam

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AU - Reinhardt, Joel

AU - Aliaga, Cesar

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N2 - The development of effective chemopreventive agents against cigarette smoke-induced lung cancer could be greatly facilitated by the availability of suitable laboratory animal models. Here we report that male Hartley guinea pigs treated with cigarette smoke by inhalation twice a day for 28 days developed preneoplastic lung lesions, including bronchial hyperplasia, dysplasia and squamous metaplasia, analogous to those found in human smokers. The lesions were accompanied by increased expression of proliferating cell nuclear antigen and activation of the serine/threonine kinase Akt in the bronchial epithelium. In contrast, no lung lesions were found in guinea pigs ('sham smoked') that were submitted to identical procedures but without cigarettes. Compared with a diet low in vitamin C (50 p.p.m.) and vitamin E (15 p.p.m.), a diet high in vitamin C (4000 p.p.m.) and vitamin E (40 p.p.m.) significantly increased the incidence of these lesions. The inclusion of 1,4-phenylenebis(methylene)selenocyanate (p-XSC), a synthetic chemopreventive organoselenium compound, in the high vitamin C-high vitamin E diet at a level of 15 p.p.m. as selenium appeared to decrease the lesion incidence. Administration of (-)-epigallocatechin gallate, a powerful green tea polyphenolic antioxidant, at 560 p.p.m. in the drinking water had no effect. As in human smokers, levels of ascorbate in blood plasma, lung, liver and the adrenal glands were significantly decreased by cigarette smoke inhalation. These results identify a relevant in vivo laboratory model of cigarette smoke-induced lung cancer, suggest that p-XSC may have activity as a chemopreventive agent against cigarette smoke-induced lung lesions and provide additional evidence that very high dietary levels of certain antioxidants can have co-carcinogenic activity in cigarette smoke-induced lung cancer.

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