| 1234 Nitrosation of Tyrosine in the Hamster Cheek Pouch | ||
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E.W.N. LAM1, R.D.C. BARLEY1, M.C. SHALLOW2, and E. PETERS1, 1University of Alberta, Edmonton, Canada, 2Dalhousie University, Halifax, Canada The relationship between smokeless tobacco use and lesions of the oral cavity, including cancer, are well known. Recently, we demonstrated that tobacco xenobiotic compounds such as smokeless tobacco, nicotine, nitrosonornicotine (NNN) and 4-(methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) release the nitric oxide free radical, ·NO. The reaction product of ·NO and superoxide (O2·-), peroxynitrite (ONOO-), is an important modulator of subcellular nitrosative damage. Objective: The purpose of this study was to describe a novel relationship between chronic tobacco xenobiotic exposure and nitrosative damage in hamster cheek pouch mucosa. Methods: Smokeless tobacco, nicotine, NNN and NNK were applied to the cheek pouch mucosa of Syrian golden hamsters 3 times per week for a 10 month period. Routine hematoxylin and eosin-stained sections of the tissues were reviewed, and immunohistochemical techniques and semi-quantitative digital image analysis were used to describe the distribution of a known protein marker of ONOO--mediated damage, 3-nitrotyrosine (3-NT) in the mucosa. Results: Light microscopic examination of smokeless tobacco-treated mucosa exhibited more high power fields showing a verruciform morphology, hyperchromatism, and nuclear and cellular pleomorphism compared with control tissues. As well, mucosa treated with NNN and NNK exhibited increased hyperchromatism and mitotic numbers compared with control tissues. 3-NT immunoreactivity was localized to the basal cell layer of the hamster cheek pouch mucosa in control animals. In mucosa chronically exposed to tobacco xenobiotics, perinuclear 3-NT staining was observed throughout the cheek pouch mucosa. Mucosa exposed to nicotine and NNK were most intensely immunoreactive to 3-NT, followed by smokeless tobacco extract- and NNN-treated tissues (p<0.005). Conclusions: Our results suggest that ONOO- is generated from tobacco xenobiotic-derived ·NO, and that 3-NT, a marker of this damage, is quantifiable in intact animal tissues. This work was supported by the Canadian Institutes of Health Research and the Alberta Heritage Foundation for Medical Research. | ||
| Seq #126 - Oral Cancer and Precancer: Diagnosis and Biomarkers 10:15 AM-11:30 AM, Thursday, 11 March 2004 Hawaii Convention Center Exhibit Hall 1-2 | ||
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