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 hamsters were divided into 6 groups. Animals in groups 1-3, each consisting of 30 hamsters, were given two s.c. injections of 20 mg/kg body weight of BOP with a one week interval as an initiation treatment. After the BOP injection, hamsters in groups 1 and 2 were respectively fed diet supplemented with 1000 or 500 ppm of PCA for 49 weeks. The animals in group 3 were treated with BOP alone. The animals in groups 4-6, each consisting of 10 hamsters, were given 1000 or 500 ppm PCA, or basal diet alone without prior BOP injection. At the termination of experimental week 52, the incidences and multiplicities of neoplastic lesions in the pancreas were comparable among the BOP-treated groups. However, the incidence of pancreatic tumors larger than 3 cm 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 which had directly invaded adjacent tissues such as the diaphragm, spleen and stomach was reduced by the PCA treatments, being significantly (p < 0.01) lower in group 2 than in group 3. Our results thus indicated that PCA can inhibit the late post-initiation or progression phase of BOP-induced pancreatic carcinogenesis in hamsters.
Nakamura
H
H
Division of Pathology, National Institute of Health Sciences, Tokyo 158-8501, Japan.
Nishikawa
A
A
Furukawa
F
F
Kasahara
K
K
Miyauchi
M
M
Son
H Y
HY
Hirose
M
M
D000230:Adenocarcinoma / Q000139:chemically induced / Q000517:prevention & control*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000037:antagonists & inhibitors* / Q000633:toxicity; D006224:Cricetinae; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005260:Female; D062385:Hydroxybenzoates / Q000494:pharmacology*; D008647:Mesocricetus; D009602:Nitrosamines / Q000037:antagonists & inhibitors* / Q000633:toxicity; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D004365:Drugs, Chinese Herbal; D062385:Hydroxybenzoates; D009602:Nitrosamines; C009091:protocatechuic acid; C013622:nitrosobis(2-oxopropyl)amine