Sequential Changes in the Cellular Redox State During 7,12-Dimethylbenz[a]anthracene-Induced Carcinogenesis in the...

Our objective was to elucidate sequential changes in the oxidant-antioxidant status during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. In designing the study, we divided hamsters into experimental and control groups. The right buccal pouches of the experimental animals were painted three times a week with a 0.5% solution of DMBA in liquid paraffin. The control animals received paraffin alone. The hamsters were killed after 1, 4, 8, 12, and 16 weeks of DMBA treatment, and the buccal pouches were examined for histopathological changes. The extent of lipid peroxidation and the status of glutathione-dependent antioxidants were evaluated in the buccal pouch, liver, and erythrocytes. Our results showed that the experimental animals developed severe hyperplasia and hyperkeratosis after 4 weeks, dysplasia after 8 weeks, and well-developed squamous cell carcinomas after 16 weeks of DMBA application. Topical application of DMBA increased lipid peroxidation in the buccal pouch up to the 8th week; there was a substantial fall after 12 weeks and significantly low levels after 16 weeks. This was accompanied by a sustained increase in reduced glutathione (GSH) and the activities of glutathione peroxidase (GPx), glutathione-S-transferase (GST), and gamma-glutamyltranspeptidase (GGT) throughout the carcinogenic progression. However, in the liver and erythrocytes, the concentrations of lipid peroxides were higher, and GSH- and GSH-dependent enzyme activities were lower than in the controls throughout the experiment. This study has revealed intrinsic differences in the cellular redox state in the target organ and host tissues of tumor-bearing animals. We suggest that measurement of lipid peroxidation and GSH-dependent antioxidants could be valuable in evaluating carcinogenic progression and the effects of putative chemopreventive agents in the hamster buccal pouch model.