Pancreatic neoplasms in an animal model: Morphological, biological, and comparative studies

Abstract

After a short latency (15 weeks), a 100% incidence of pancreatic neoplasms was induced i n Syrian golden hamsters, following the administration of 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN). D a t a extracted from reports of h u m a n pancreatic neoplasms were compared with findings relative to the induced neoplasms. The latter resembled h u m a n pancreatic tumors, in both biological and morphological aspects. The authors greatly appreciate the encouragement and critical advice of Dr. P. Shubik.Received for publication July 2, 1974. low rates of cancer production,1~~1~~*0~43~~1 3 ) MATERIALS AND METHODSRandom bred, 8-week-old Syrian golden hamsters from the Eppley colony were kept under standard laboratory conditions and given Wayne Pellet diet and water ad libitum.The animals, in three groups of 20 males and 20 females each, received weekly subcutaneous injections for life of 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN) at the following doses:Group 1, 500 mg/kg body weight; Group 2, 250 mg/kg b.w.; and Group 3, 125 mg/kg b.w. Twenty male and 20 female controls received the olive oil solvent and were sacrificed a t the experiment's 44th week, when the last DHPNtreated animal died. Following complete autopsies, tissues were fixed in 10% buffered formalin; Paraplast sections were stained with hematoxylin and eosin.Step sections and special stainings (using periodic acid-Schiff, Alcian blue, Masson's trichrome, and Bodian's and Gomori's silver methods) were prepared from each pan'creas. The effective number of animals corresponds to the number of pancreases which could be evaluated histologically. The tumor latencies were determined in correlation with the length of survival time dating from the experiment's beginning. Table 1 contains the data concerning pathologic findings, number of animals, their average survival times, body weights, and the incidence and latency of the pancreatic n e e plasms. Treated animals developed diarrhea and presented weight losses at about 16 weeks 379 RESULTS

Are there Hidden (Latent, Silent, Occult) Pancreatic Cancers?

“…They had several noteworthy features, which, in many aspects, resembled findings in the hamster pancreatic carcinoma model [21][22][23]. The destruction of islets by cancer cells in both cases was striking and correlated with some experimental observations.…”

“…The destruction of islets by cancer cells in both cases was striking and correlated with some experimental observations. In the hamster, pancreatic carcinoma model, ductal adenocarcinomas arise from ductal and ductular cells but develop predominantly within islets [19][20][21]. As in humans, the intraductal tumors grow slowly, extend and remain within the ductal boundary for some time.…”

“…As in humans, the intraductal tumors grow slowly, extend and remain within the ductal boundary for some time. By contrast, the tumors of the experimental model that develop within islets are highly malignant from their inception [19][20][21]. The occurrence of malignant glandular structures within human islets has also been observed [19,20], but the derivation of malignant cells from within islets is unknown.…”

Challenges and advances in mouse modeling for human pancreatic tumorigenesis and metastasis

“…The most widely used and studied model is Syrian gold hamsters intraperitoneally injected with N -nitrosobis(2-oxopropyl)amine [23–25]. More recent approaches involve the uses of azaserine in rats [26–28] and 7,12-dimerthylbenzanthracene in mice [29].…”

Growth inhibition of experimental pancreatic cancers and sustained reduction in epidermal growth factor receptors during therapy with hormonal peptide analogs

“…Because of the presence of speci®c receptors on tumor cells, the sensitivity to growth factors and various hormones, the nitrosamine-induced pancreatic cancers in hamsters represent an appropriate model for the study of human ductal pancreatic carcinoma and are suitable for evaluating the eects of various treatments (Pour et al 1975;Takiyama et al 1990;Szepeshazi et al 1993Szepeshazi et al , 1994. Using this model, we demonstrated strong tumor inhibition after chronic treatment with agonist [DTrp 6 ]LH-RH (Szende et al 1990a, b), LH-RH antagonist Cetrorelix (SB-75) (Szende et al 1990a;Szepeshazi et al 1991aSzepeshazi et al , 1994, somatostatin analog RC-160 (Szende et al 1990b;Szepeshazi et al 1991b) and bombesin antagonist RC-3095 (Szepeshazi et al 1991b(Szepeshazi et al , 1993(Szepeshazi et al , 1996.…”