There is evidence for synergy between tobacco and alcohol in the etiology of oral cancer but the reason for such an effect is unclear. One possible explanation is that alcohol enhances the penetration of carcinogens through the oral lining. We measured the permeability in vitro of three regions of porcine oral mucosa to the tobacco associated carcinogen, nitrosonornicotine (NNN) alone and in the presence of 5% or 50% ethanol. 50% ethanol did not significantly alter the permeability of oral mucosa to NNN except for buccal mucosa, where it was reduced. However, there was a significant increase in the permeability of gingiva and floor of mouth mucosa (but not buccal mucosa) in the presence of 5% ethanol; this increase occurred after far shorter exposures for floor of mouth than for gingiva. These results accord well with studies showing (a) that the Door of mouth is a “high risk area” for oral carcinoma and (b) that there is an increased relative risk of oral cancer for heavy smokers and drinkers and, in particular, for those individuals who consume beverages with a low alcohol content.
The permeability of porcine skin and keratinized and nonkeratinized oral mucosa to tritium-labeled water and horseradish peroxidase (HRPO) was determined using perfusion chambers. Small blocks from each tissue were also incubated with HRPO and the extent of penetration visualized microscopically; this enabled measurements to be made of the thickness of the permeability barrier to this water-soluble tracer. Results obtained after inverting the oral mucosa in the chambers or adding metabolic inhibitors indicated that both compounds diffuse across the tissue. The permeability constants derived directly in the study showed that skin was less permeable than oral mucosa and that the floor of the mouth was significantly more permeable than all other regions. When these constants were normalized in terms of a standard permeability barrier thickness and the different tissues compared, the values obtained for skin were again less than those of the oral regions but, of these, the buccal mucosa was significantly higher. The difference in permeability between epidermis and keratinized oral epithelium may be due to differences in the volume density of membrane-coating granules known to exist between the tissues; differences between the oral mucosal regions may reflect differences in the nature of the intercellular barrier material.
The gingival overgrowth obtained after maintaining ferrets on PHT appeared to be due entirely to the effect of the drug, for inflammation induced by banding had no influence on the action of PHT in eliciting the overgrowth. The significant change observed was an increase in relative volume of interstitial material (ground substance) in response to PHT. Although there was no appreciable alteration in numbers of cells present in the lesion, PHT had a significant effect on the ultrastructure of fibroblasts. These cells showed a decrease in the relative volume of phagosomes, although organelles concerned with synthesis (the rough endoplasmic reticulum and Golgi zones) were not affected. This suggests that the relative increase in ground substance may reflect decreased breakdown of extracellular material within fibroblasts, while synthetic activity is maintained at a constant level. As a consequence, there is an increase in connective tissue volume--an increase which is manifested as an overgrowth.
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