Inhibitory effects of protocatechuic acid on the post-initiation phase of hamster pancreatic carcinogenesis induced by N-nitrosobis (2-oxopropyl)amine

The chemopreventive effects of protocatechuic acid (PCA) were investigated during the post-initiation stage of the N-nitrosobis(2-oxopropyl)amine (BOP )-initiated hamster pancreatic tumorigenesis model. Female 5-week-old hamst ers were divided into 6 groups. Animals in groups 1-3, each consisting of 3 0 hamsters, were given two sc injections of 20mg/kg body weight of BOP with a one week interval as an initiation treatment. After the BOP injection, h amsters in groups I and 2 were respectively fed diet supplemented with 1000 ol 500 ppm of PCA for 49 weeks, The animals in group 3 were treated with B OP alone. The animals in groups 4-6, each consisting of 10 hamsters, were g iven 1000 or 500 ppm PCA, or basal diet alone without prior BOP injection. At the termination of experimental week 52, the incidences and multipliciti es of neoplastic lesions in the pancreas were comparable among the BOP-trea ted groups. However the incidence of pancreatic tumors larger than 3cm was significantly lower in the PCA-treated high dose groups than in the control group (p< 0.05). Moreover the incidence of advanced pancreatic cancers whi ch had directly invaded adjacent tissues such as the diaphragm, spleen and stomach was reduced by the PCA treatments, being significantly (p<0.01) low er in group 2 than in group 3. Our results thus indicated that PCA can inhi bit the late post-initiation or progression phase of BOP-induced pancreatic carcinogenesis BI hamsters.