PCNA in palate and tongue mucosal dysplastic lesions induced by topically applied 4NQO in desalivated rat.
OBJECTIVE
Saliva has been suggested to have a protective role against carcinogens in the oral cavity in animals. Water-soluble 4NQO is a suitable carcinogen to use in examining the role of saliva in oral cancer. The purpose of this study was to follow the changes induced by the carcinogen at the molecular level, as well as the effect of lack of saliva on these changes.


METHODS
Topical application to the palate of a 0.5% 4NQO solution dissolved in glycol was used for 4 months to induce malignant transformation in a desalivated rat model. Histomorphometric analysis of proliferating cell nuclear antigen (PCNA), a cell cycle regulator and a proliferation marker, was performed.


RESULTS
Manifestation of PCNA significantly increased as the observed histologic changes progressed from hyperkeratosis, to mild or moderate dysplasia, severe dysplasia and squamous cell carcinoma. Differences in manifestation of PCNA among the diagnostic groups was significant (p< 0.05). In the desalivated group, PCNA expression was significantly higher than in control and normal groups, in both tongue and palate after 2 and 4 months (p< 0.05).


CONCLUSIONS
An unknown component of saliva has a temporary anti-carcinogenic protective effect, which can both delay and decrease the level of proliferation induced by the carcinogen 4NQO. The specific salivary component and the mechanism by which this protective effect is rendered are yet to be discovered.
Kaplan
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Department of Oral Pathology and Oral Medicine The Maurice and Gabriela Goldschleger School of Dental Medicine Tel Aviv University, Tel Aviv ISRAEL. ddayan@post.tau.ac.il
Hochstadt
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T
Dayan
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D015112:4-Nitroquinoline-1-oxide / Q000008:administration & dosage*; D000287:Administration, Topical; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage*; D008297:Male; D009061:Mouth Mucosa / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D010159:Palate / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D014059:Tongue / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology
D002273:Carcinogens; D018809:Proliferating Cell Nuclear Antigen; D015112:4-Nitroquinoline-1-oxide