Experimental Oral Carcinogenesis With Particular Reference to Premalignant Lesions

MacDonald, Donald Gordon (1973) Experimental Oral Carcinogenesis With Particular Reference to Premalignant Lesions. PhD thesis, University of Glasgow.

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Abstract

Squamous cell carcinoma of the oral cavity is a cause of significant morbidity and mortality in Scotland and in many other parts of the world. Prom a pathologist's viewpoint one of the important problems relating to this disease is in the diagnosis of early lesions particularly those in the premalignant phase which can precede tumour development. The aim of the work described in this thesis was to advance knowledge of the premalignant phase in the development of squamous cell carcinoma of the mouth. It was desirable to use an experimental animal oral cancer model in this study and a preliminary evaluation of the standard technique for inducing hamster cheek pouch carcinomas was made. This technique gave poor localisation of the response to carcinogen application and also had the disadvantage of producing severe ulceration. A new technique of tumour induction in hamster cheek pouch was devised to overcome these problems. This technique was then used to produce premalignant lesions in the hamster cheek pouch which were biopsied and then followed to relate the subsequent progress to the histological changes seen at the time of biopsy. A detailed objective quantitative analysis of the changes of cellular atypia which characterise the premalignant lesions was made according to the technique of Smith and Pindborg (1969). It was shown that this technique was a good prognostic indicator in hamster cheek pouch lesions. In order to examine the validity of applying the results obtained in the hamster cheek pouch to human oral lesions comparison of human and hamster premalignant lesions was undertaken. Although a few obvious differences were noted, detailed comparisons of the cellular atypia as evaluated by the Smith and Pindborg (1969) technique indicated that the human and hamster premalignant lesions were closely similar. It was concluded that the Smith and Pindborg (1969) technique should be a reliable prognostic indicator in human oral lesions. A study of the histological features present in human oral lesions indicated that although the features usually described as characterising squamous cell carcinomas were most frequent in these lesions they were also demonstrable in some non-neoplastic oral mucosal lesions. Some authors have criticised the hamster cheek pouch tumour model on the grounds that the cheek pouch is not exposed to the same environment as the mouth proper. Evaluation was therefore made of the early responses to carcinogen application at three truly intraoral sites in the hamster. The areas studied were in the "drainage area" of the lingual sulcus and the specific sites examined were the ventral surface of tongue, the lateral surface of tongue and the lingual gingivae. Premalignant changes were observed at all three sites although these developed less rapidly than in the case of cheek pouch lesions. The site showing the most consistent and marked response was the ventral surface of the tongue and it was felt that this was the site which most merited further study. The quantitative techniques used in the earlier analysis of premalignant changes were fairly crude and it was felt desirable to derive more accurate quantitative data. The problems of applying stereologic methods to oral mucosa were studied and these methods were applied to normal and carcinogen treated ventral tongue epithelium in the hamster. The investigation was concerned mainly with basal cells and the basement membrane zone. At a light microscopic level, quantitation of the cell compartments of the epithelium was undertaken and this gave a measure of the atrophy in carcinogen treated epithelium. The nucleo-cytoplasmic ratios of basal cells were studied at a low power electron microscope level and at a higher power the basement membrane zone and in particular hemides- mosomes were studied. Control sections demonstrated a previously unrecorded "horizontal" anisotropy in tongue epithelium in that hemidesmosomes were shown to be less frequent, but of longer profiles on average in sections in the long axis as opposed to the short axis of the tongue. In carcinogen treated epithelium a further reduction in numbers of hemidesmosomes was observed, but these had longer profiles in section than hemidesmosomes in control tissues. The derivation of valid quantitative data by stereologic techniques can only be achieved after a number of requirements concerning such factors as random selection, orientation and the limitations of particular measuring techniques have been satisfied. This study has shown how this may be achieved. It. is suggested that these methods could form a basis for future quantitative studies of other cell changes found in premalignancy with a view to evaluating their diagnostic potential in human lesions.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Dentistry, Pathology
Date of Award: 1973
Depositing User: Enlighten Team
Unique ID: glathesis:1973-78639
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 30 Jan 2020 15:07
Last Modified: 30 Jan 2020 15:07
URI: http://theses.gla.ac.uk/id/eprint/78639

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