Sequential expression of placental glutathione S-transferase (GST-P) during DMBA-induced hamster buccal pouch squamous cell carcinogenesis

The aim of the present study was to investigate the sequential expression of placental glutathione S-transferase (GST-P) during 7,12-dimethylbenza]anthracene (DMBA)-induced hamster buccal pouch squamous cell carcinogenesis. Both immunohistochemical and immunoblot analyses were employed to detect the epithelial GST-P in hamster buccal pouch mucosa over a 15-week treatment regimen. No GST-P positivity was demonstrated in the pouches of the control group. GST-P positive cells were first noted as early as 1 week after DMBA applications. A gradual increase in both the mean number and size of GST-P-positive foci was noted in the first 12 experimental weeks, but a plateau level was approached thereafter. The early GST-P-positive-area were located in the basal layer, or occasionally in the middle layer, of DMBA-treated hamster buccal pouch mucosa. Later, the stained sites became enlarged and were scattered randomly in different layers or in the whole thickness of the dysplastic and non-dysplastic epithelium. The keratin layer was only occasionally involved during the first 12 weeks of DMBA treatment but positive staining was more noticeable in the final stage of the experiment. Both exophytic (8-12 weeks) and invasive (13-15 weeks) squamous cell carcinomas showed GST-P positivity, in both cytoplasmic and nuclear components. Immunoblot analysis revealed no band in the crude tissue extracts of the control pouches whereas GST-P polypeptide of molecular weight approximately 26 kD was demonstrated in DMBA-treated pouches over the whole 15-week treatment regimen. Results of the present work indicate that GST-P is a stable and persistent label for almost all of the carcinogen-altered cells during DMBA-induced hamster buccal pouch carcinogenesis. Immunohistochemically detectable GST-P may be a potential marker throughout oral chemical carcinogenesis.