Journal Article

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 and Cesar Aliaga

in Carcinogenesis

Volume 26, issue 3, pages 605-612
Published in print March 2005 | ISSN: 0143-3334
Published online March 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh341
Induction of preneoplastic lung lesions in guinea pigs by cigarette smoke inhalation and their exacerbation by high dietary levels of vitamins C and E

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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.

Keywords: AA, ascorbic acid; dehydro-AA, dehydroascorbic acid; EGCG, (−)-epigallocatechin gallate; HPLC-EC, high performance liquid chromatography with electrochemical detection; NNK, 4-(methylnitrosamino)-1-(3-pyridye)-1-butanone; PCNA, proliferating cell nuclear antigen; p-XSC, 1,4-phenylenebis (methylene) selenocyanate; VE, vitamin E.

Journal Article.  6688 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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