CHEMOPREVENTION OF URINARY-BLADDER CARCINOGENESIS BY THE NATURAL PHENOLIC COMPOUND PROTOCATECHUIC ACID IN RATS

The modifying effect of dietary administration of protocatechuic acid (PCA) during the initiation and postinitiation phases on N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced bladder carcinogenesis was investigated in male F344 rats. Animals were divided into nine groups and groups 1-7 were given 0.05% BBN in drinking water for 6 weeks to induce bladder neoplasms. Rats in groups 2, 3 and 4 were fed diets containing 500, 1000 and 2000 p.p.m. PCA respectively for 8 weeks, starting 1 week before BBN exposure. Groups 5, 6 and 7 were fed the PCA-containing diets at three dose levels for 33 weeks. Group 8 was fed the diet containing 2000 p.p.m. PCA alone throughout the study. Group 9 was given tap water without BBN and the basal diet without PCA and served as an untreated control. At 41 weeks after the start, all animals were killed. The incidence of bladder tumors and preneoplastic lesions, and cell proliferation activity estimated by the numbers of silver-stained nucleolar organizer regions proteins (AgNORs) and proliferating cell nuclear antigen (PCNA)-immunoreactive cells were compared among the groups. PCA administration at 1000 and 2000 p.p.m. during the initiation and postinitiation phases significantly decreased the carcinoma incidence in a dose-dependent manner. Also, PCA at all doses given during either initiation or postinitiation phases reduced the development of the preneoplastic lesions. PCA feeding significantly reduced the numbers of AgNORs and PCNA-positive cells in the non-lesional transitional epithelium, preneoplasms, and neoplasms in the urinary bladder of rats treated with BBN. These results indicate that dietary administration of PCA is quite effective in preventing BBN-induced bladder carcinogenesis.