title: Induction of preneoplastic lung lesions in guinea pigs by cigarette smoke inhalation and their exacerbation by high dietary levels of vitamins C and E.
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.
authors.affiliation: Institute for Cancer Prevention, Valhalla, NY, USA. efiala@att.net
authors.forename: Emerich S
authors.initials: ES
authors.lastname: Fiala
authors.forename: Ock Soon
authors.initials: OS
authors.lastname: Sohn
authors.forename: Chung-Xiou
authors.initials: CX
authors.lastname: Wang
authors.forename: Eleanore
authors.initials: E
authors.lastname: Seibert
authors.forename: Junji
authors.initials: J
authors.lastname: Tsurutani
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Dennis
authors.forename: Karam
authors.initials: K
authors.lastname: El-Bayoumy
authors.forename: Rama S
authors.initials: RS
authors.lastname: Sodum
authors.forename: Dhimant
authors.initials: D
authors.lastname: Desai
authors.forename: Joel
authors.initials: J
authors.lastname: Reinhardt
authors.forename: Cesar
authors.initials: C
authors.lastname: Aliaga
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000097:blood; D004032:Diet; D004789:Enzyme Activation; D006168:Guinea Pigs; D007150:Immunohistochemistry; D019570:Inhalation Exposure; D008175:Lung Neoplasms / Q000209:etiology*; D011230:Precancerous Conditions / Q000209:etiology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana; D014810:Vitamin E / Q000008:administration & dosage*
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; D012906:Smoke; D014810:Vitamin E; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D001205:Ascorbic Acid