The hamster cheek pouch (HCP) serves as an excellent model system not only for the studies on initiation and promotion but also for the modulation of experimental oral carcinogenesis. In our studies, HCPs treated with 7,12-dimethylbenz[a]anthracene (DMBA) showed both cheek pouch and stomach papillomas. Utilizing this model system, we tested and compared the modulatory effects of snuff, retinoic acid, and beta-carotene on the incidence of tumors and the keratin expression pattern. HCPs treated with snuff, either alone or in combination with DMBA, resulted in stomach papillomas. HCPs treated with snuff showed no cheek pouch tumors, and those treated with snuff and DMBA showed only 10-15% tumor incidence. Both beta-carotene and retinoic acid showed a total inhibition of DMBA-induced carcinogenesis in the HCP as well as in the stomach. The keratin expression pattern showed alterations depending on the experimental conditions.
Tobacco and its related compounds, including snuff, have been implicated in oral cancers. Tobacco-specific nitrosamines have been shown to be the causative agents present in tobacco and its related compounds. Both, N-nitrosonornicotine (NNN) and its butanone derivative (NNK) are carcinogenic in animals. In our in vitro studies using embryonic mouse tongue epithelial cells, NNN is linked to an increase in [3H]dT uptake along with a concomitant increase in ornithine decarboxylase and aryl hydrocarbon hydroxylase activities. NNK, the more potent compared to NNN, causes a further increase in [3H]dT uptake, cell count and ornithine decarboxylase activity. However, aryl hydrocarbon hydroxylase behaves differently in cultures treated with NNK compared to those treated with NNN. Snuff extract has an overall inhibitory effect on cell count, [3H]dT uptake, and ornithine decarboxylase and aryl hydrocarbon hydroxylase activities when administered either alone or in combination with NNN and NNK. How the inhibitory effect of snuff in the presence of tobacco-specific nitrosamines is involved in oral carcinogenesis should be further investigated.
The altered pattern in the expression of keratin proteins as a function of tumour progression was studied in the hamster cheek pouch and compared the changes with electron microscopic observations using DMBA as a carcinogen. In the case of hyperplasia and well developed tumours a conspicuous loss of 67 K and an increase in 46 K was observed compared to the controls. The increased expression of low molecular weight keratins during tumour growth is well supported by the enhanced expression of tonofilament bundles, electron microscopically. This study suggests a triangular relationship between the presence of low molecular weight keratins-enhanced expression of tonofilament bundles and the undifferentiated nature of the oral tumours.
Experiments were performed to study the early and late ultrastructural changes during hamster cheek pouch carcinogenesis using a regimen of topical application of 9,10 dimethyl-1-1-2 benzanthracene (DMBA) twice a week in liquid paraffin oil. The DMBA was administered for a period of 2 and 4 1/2 months. Hamsters exposed to DMBA for 2 months developed moderate precancerous changes, whereas the hamsters treated with DMBA for 4 1/2 months developed frank and multiple oral tumors with a cauliflower appearance. The ultrastructural pathological changes seen were considerably increased at 4 1/2 months compared with a 2 month period of DMBA treatment. Untreated and solvent control hamsters cheek pouch treated for 2 and 4 1/2 months with liquid paraffin oil alone did not show any premalignant or malignant changes during this period.
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