INHIBITORY EFFECTS OF DIETARY PROTOCATECHUIC ACID AND COSTUNOLIDE ON 7,12-DIMETHYLBENZ[A]ANTHRACENE-INDUCED HAMSTER-CHEEK POUCH CARCINOGENESIS

The modifying effects of dietary exposure to two natural products, pro tocatechuic acid (PCA) and costunolide during the development of neopl asms in oral carcinogenesis initiated with 7,12-dimethylbenz[a]anthrac ene (DMBA) were investigated in male Syrian golden hamsters. All hamst ers except those in the test chemical alone and control groups receive d DMBA (0.5%) in mineral oil to the right buccal pouch 3 times per wee k for 4 or 6 weeks. At 13 weeks of age, the groups exposed to DMBA wer e fed diet containing PCA or costunolide at a dose of 0.2 g/kg diet (2 00 ppm) for 17 weeks. The other groups consisted of hamsters given min eral oil alone for 6 weeks, or given 200 ppm PCA or costunolide alone, or untreated. All animals were necropsied at the termination of the e xperiment (week 24). PCA or costunolide significantly decreased the tu mor burden (P< 0.001-P < 0.05) and the extent of dysplastic areas (%) (P < 0.001-P < 0.05). PCA significantly decreased the mean number of A gNORs/nucleus (P < 0.05). The BrdUrd-labeling index was reduced by die tary administration of test compounds, though not significantly. These results suggest that PCA and costunolide inhibited hamster buccal pou ch carcinogenesis and such inhibition may be related to suppression of cell proliferation in the buccal mucosa. It was also found that telom erase activity expressed in neoplastic and preneoplastic lesions of ha mster buccal pouch epithelium after DMBA treatment correlated with the histopathological degree of malignancy.