Induction of preneoplastic lung lesions in guinea pigs by cigarette smoke inhalation and their exacerbation by high dietary levels of vitamins C and E
| Autor: | Joel Reinhardt, Dhimant Desai, Emerich S. Fiala, Rama S. Sodum, Ock Soon Sohn, Chung Xiou Wang, Junji Tsurutani, Cesar Aliaga, Phillip A. Dennis, Eleanore Seibert, Karam El-Bayoumy |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Vitamin
Cancer Research Pathology medicine.medical_specialty Lung Neoplasms medicine.medical_treatment Guinea Pigs Physiology Ascorbic Acid Protein Serine-Threonine Kinases Lesion chemistry.chemical_compound Proliferating Cell Nuclear Antigen Proto-Oncogene Proteins Smoke Tobacco medicine Animals Vitamin E Lung cancer Inhalation Exposure Vitamin C Inhalation business.industry General Medicine medicine.disease Ascorbic acid Immunohistochemistry Squamous metaplasia Diet Enzyme Activation chemistry medicine.symptom business Precancerous Conditions Proto-Oncogene Proteins c-akt |
| Zdroj: | Carcinogenesis. 26:605-612 |
| ISSN: | 1460-2180 0143-3334 |
| DOI: | 10.1093/carcin/bgh341 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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