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Studies of tumor promoters and drug-metabolic enzymes in hamster buccal pouch mucosa

University of British Columbia

Lack of tumor promoters has been the major obstacle in the use of the hamster buccal pouch mucosa (HBPM) model. Two experiments were designed to investigate the effects of two new mouse skin tumor promoters, okadaic acid (OA) and methyl methanesulfonate (MMS), on HBPM. Short term effects of OA were studied. A single application of10 1.1.g of OA in 0.1 ml of acetone produced marked inflammation as well as an increased mitotic rate (p<0.01) as compared to that of the control. It, therefore, seems that OA possesses some essential properties of tumor promoter. Long term study is necessary to prove that it is a potent tumor promoter in HBPM. Tumor promoting effects of MMS were examined in a long term experiment. 25 hamsters were divided into 3 groups. In group I, pouches of 10 hamsters were initiated with 7,12-dimethylbenzanthracene (DMBA), then promoted with MMS for 10weeks. In group II, pouches of 10 hamsters were initiated with MMS and promoted with MMS. In group III, pouches of 5 hamsters were initiated with DMBA (right pouches) or MMS (left pouches), and promoted with acetone. The results showed that MMS had moderate tumor promoting effects but no tumor initiating effects in the model. Gamma-glutamyl transpeptidase (GGT) and placentalglutathione S-transferase (GST-P) have been found to be increased during HBPM carcinogenesis. Whether such increases are oncofetal remains to be answered. There are few studies on the normal distribution of GGT and GST-P in hamster tissues. One experiment was designed to study their tissue distributions during the development of hamster pouches and several selected organs and tissues. The results showed no GGT and GST-P activities in hamster pouches during their development. The expression of GGT and GST-P activities during HBPM carcinogenesis may represent an acquired genetic alteration instead of oncofetal reversion. GGT was found in epithelial cells, particularly those with 'brush borders', in several organs and tissues, supporting the hypothesis that GGT may participate in amino acid transportation. Rarely, GGT was also noted in mensenchymal cells. GST-P was observed in few organs and only expressed in epithelium.

Thesis/Dissertation

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2008-09-22

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http://hdl.handle.net/2429/2343

Dental Science

University of British Columbia

UBCV

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