In order to investigate the relationship between GGT histochemical activity and cell proliferation during cheek pouch carcinogenesis in the hamsters, a combination of GGT histochemical and BrdU immunohistochemical analysis was performed.
One or both cheek pouches of male golden hamsters were treated topically with 0.5% 9, 10-dimethyl-1, 2-benzanthracene (DMBA) in mineral oil over 20 weeks to produce numerous epithelial lesions at the various stages of neoplastic development. GGT histochemical activity was detected in both dysplastic and nondysplastic regions of the epithelium. GGT staining was frequently sharply demarcated from the adjacent unstained epithelium and usually extended from the basal cell layers to the superficial keratinizing layer at the early time periods of carcinogenesis. The GGT-positive areas showed the increased number and irregular distribution of BrdU-positive cells, which was not only present in the basal layer but also in 2-3 layers above it. The adjacent unstained epithelium showed a regular distribution of Brd Upositive cells limited to the basal layer. A good correlation was observed between the presence of GGT-positive areas and proliferative BrdU-positive cells, (S phase cells) during the early stage of carcinogenesis.
Papillomas and well differentiated squamous cell carcinomas had patched GGT histochemical activity mostly in superficial keratin and dead keratinized cells. The number of BrdUpositive cells in GGT-positive areas was lower than those in the GGT-negative areas of the same papillomas. BrdU-positive cells were primarily found in the peripheral areas of the cancer nest of well differentiated squamous cell carcinomas. The cancer nest of poorly differentiated squamous cell carcinomas displayed very rarely GGT histochemical activity. BrdU positive cells were irregularly distributed throughout the cancer nest of these carcinomas. There was no correlation between GGT histochemical activity and cell proliferation in papillomas and squamous cell carcinomas during the late stage being different from that observed between GGT histochemical activity and cell proliferation in various lesions in the early stage of carcinogensis.
