Pancreatic intraepithelial neoplasia and ductal adenocarcinoma induced by DMBA in mice: effects of alcohol and caffeine

PURPOSE: To evaluate the effects of alcohol and caffeine in a pancreatic carcinogenesis mouse model induced by 7,12-dimethylbenzantracene (DMBA), according to the PanIN classification system. METHODS: 120 male, Mus musculus, CF-1 mice were divided into four groups. Animals received either water or caffeine or alcohol or alcohol + caffeine in their drinking water. In all animals, 1 mg of DMBA was implanted into the head of the pancreas. After 30 days, euthanasia was performed; excised pancreata were then fixed in formalin, stained with hematoxylin-eosin and categorized as follows: normal ducts, reactive hyperplasia, PanIN-1A, PanIN-1B, PanIN-2, PanIN-3 or adenocarcinoma. RESULTS: PanIN lesions were verified in all groups. Adenocarcinoma was detected in 15 percent of animals in the caffeine group, 16.6 percent in the water group, 23.8 percent in the alcohol + caffeine group and 52.9 percent in the alcohol group (P<0.05). CONCLUSIONS: The experimental pancreatic carcinogenesis mouse model using DMBA effectively induces PanIN lesions and pancreatic adenocarcinoma. This study verified the association between alcohol use and pancreatic adenocarcinoma; caffeine did not present the same effect.

OBJETIVO: Avaliar os efeitos do álcool e da cafeína na carcinogênese pancreática induzida pelo 7,12-dimetilbenzantraceno (DMBA) em camundongos, descrevendo as lesões de acordo com a classificação das neoplasias pacreáticas intraepiteliais (PanIN). MÉTODOS: 120 camundogos machos, Mus musculus, CF-1 foram divididos em quatro grupos. Animais receberam água ou cafeína ou álcool ou álcool + cafeína para beber. Em todos animais, 1 mg de DMBA foi implantado na cabeça do pâncreas. Após 30 dias, eutanásia foi realizada, o pâncreas foi removido, fixado em formalina e corado com hematoxilina e eosina sendo classificado em: ductos normais, hiperplasia reativa, PanIN-1A, PanIN-1B, PanIN-2, PanIN-3 ou adenocarcinoma. RESULTADOS: Neoplasias pancreáticas intraepiteliais foram encontradas em todos grupos. Adenocarcinoma foi detectado em 15 por cento dos animais do grupo cafeína, 16,6 por cento do grupo água, 23,8 por cento do grupo álcool + cafeína e 52,9 por cento do grupo álcool (P<0,05). CONCLUSÕES: O modelo experimental de carcinogênese pancreática em camundongos utilizando DMBA induz neoplasias pancreáticas intraepiteliais (PanIN) e adenocarcinoma pancreático. Este estudoverificou associação entre álcool e adenocarcinoma pancreático, enquanto a cafeína não demonstrou este efeito.

Nuclear magnetic resonance spectroscopy in pancreatic disorders

Nuclear magnetic resonance spectroscopy (NMRS) is a powerful technique that enables continuous monitoring of biochemical processes in tissues and organs in a non-invasive manner. A model of isolated perfused rat pancreas, suitable for NMRS studies, was developed. Acute pancreatitis was induced by injections of either 0.5 me 5 per cent sodium taurocholate (TC) into the bile ducts, or 1.0 ml 10 per cent TC injection into the pancreatic parenchyma. Phosphorus (P) NMRS of experimental pancreatitis were characterized by a transient signal at -0.18ñ0.04 ppm which was assigned as solubilized lecithin, and cana be used as an indicator of the early also found during acute pancreatitis,and paralleled the extension of the pathological damage. The role of NMRS in pancreatic cancer diagnosis and its treatment were assessed in three moeels of pancreatic neoplasms. Perfused MIA PaCa-2 human pancreatic cancer cells, subcutaneously implanted pancreatic tumors in hamster, and pancreatic tumors induced in-situ in rats by direct application of the carcinogen 7,12-dimethil benzanthracene, were studied by phosphorus (P), sodium (Na) and proton (H) NMRS. P spectra of pancreatic cancer were similar in both the normal pancreas and the pancreatic tumors (39-40 mmol/g wet weight)...