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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To examine the effect of cholecystokinin (CCK) on pancreatic carcinogenicity in the hamster model, two sets of experiments were carried out. In one study, CCK (20 IDU/kg body wt) was given 3 h before, simultaneously with or 3 h after a single dose (20 mg/kg body wt) of N-nitrosobis(2-oxopropyl)amine (BOP). In another experiment, hamsters were treated similarly except that both CCK (20 IDU/kg body wt) and BOP (2.5 mg/kg body wt) were given weekly for 20 weeks. The results showed that CCK in the first experiment (single BOP dose) inhibited pancreatic cancer induction in a statistically significant fashion when given either 3 h prior to (P less than 0.05) or simultaneously with BOP (P less than 0.0005); however, CCK, when administered after BOP did not alter the cancer incidence as compared with hamsters treated with BOP alone. In the second experiment (chronic BOP treatment) the pattern and the incidence of pancreatic tumors were not affected by CCK.
Carcinogenesis 1988 Apr
PMID:Effect of cholecystokinin on pancreatic carcinogenesis in the hamster model. 283 67

The effect of chronic ethanol ingestion on dietary fat-promoted pancreatic carcinogenesis was investigated in rats and hamsters. Rats were given a single i.p. injection of 30 mg azaserine per kg body wt at 19 days of age. Hamsters were injected s.c. with 20 mg N-nitrosobis(2-oxopropyl)amine (BOP) per kg body wt at 6 and 7 weeks of age. The animals were fed a semi-purified diet high in unsaturated fat (25% corn oil) either separately or in combination with ethanol. Ethanol was provided in drinking water at a concentration of 10% (w/v). A separate group maintained on a diet low in unsaturated fat (5% corn oil) was included as extra controls. The rats and hamsters were given their diets and received ethanol via their drinking water after treatment with carcinogen. Terminal autopsy of rats was 15 months after azaserine treatment and of hamsters 12 months after the last injection with BOP. Dietary fat was found to enhance pancreatic carcinogenesis in both rats and hamsters. In rats, ethanol slightly enhanced the multiplicity but not the incidence of malignant tumours, while in hamsters ethanol did not show any modulating effect on dietary fat-promoted carcinogenesis. It was concluded that dietary fat-promoted pancreatic carcinogenesis as observed in the animal models applied is not significantly modulated by chronic ethanol ingestion.
Carcinogenesis 1989 Mar
PMID:Modulation of dietary fat-promoted pancreatic carcinogenesis in rats and hamsters by chronic ethanol ingestion. 292 93

The effect of dietary fat and ethanol and their interactions on the development of putative, preneoplastic foci in exocrine pancreas was investigated in rats and hamsters. Rats were given a single i.p. injection of 30 mg azaserine per kg body wt at 19 days of age. Hamsters were injected s.c., with 20 mg N-nitrosobis(2-oxopropyl)amine (BOP)/kg body wt at 6 and 7 weeks of age. The animals were fed a low fat (LF) control diet (5% corn oil) or a high fat (HF) diet (25% corn oil). Ethanol was provided in drinking water at a 15% (w/v) concentration. The animals were given the respective diets and ethanol after the treatment with carcinogen. At 4 months post-initiation, the pancreata were quantitatively examined for the number and size of preneoplastic foci. In rats, acidophilic as well as basophilic foci were subject to modulation by HF and ethanol. The results point to a specific promoting effect of unsaturated fat on the growth potential of azaserine-induced acidophilic acinar cell foci in rat pancreas. There was no evidence of an interaction between HF and ethanol as far as acidophilic foci are concerned. Evaluation of the number and size of the basophilic foci demonstrated an enhancing effect of ethanol on the modulation of pancreatic carcinogenesis by fat, pointing to a possible interaction between these two lifestyle factors. This suggestion was supported by the finding that six out of 20 rats in the HF with ethanol group exhibited a carcinoma in situ, whereas in the HF and in the ethanol group such an advanced lesion was found in one animal only. Unlike in rats, ethanol had no modulating effect on number and growth of putative, preneoplastic lesions in hamsters, either in combination with LF or in combination with HF. A HF diet, however, caused a significant increase in number as well as an increase in percentage of pancreatic tissue occupied by early lesions induced in hamster pancreas by BOP.
Carcinogenesis 1986 Sep
PMID:Modulation of putative preneoplastic foci in exocrine pancreas of rats and hamsters. I. Interaction of dietary fat and ethanol. 294 27

Clinical studies suggest that diabetes mellitus may predispose to the development of pancreatic cancer. The current study investigated the effect of experimental diabetes on the susceptibility of the Syrian hamster to the induction of exocrine pancreatic carcinoma by the carcinogen BOP. Diabetes was induced with the B-cell toxin streptozotocin. Three groups of animals were studied: nondiabetic control animals and animals with streptozotocin-induced diabetes, and a third group of animals in which the diabetogenic effect of streptozotocin was blocked with nicotinamide. Streptozotocin-induced diabetes significantly inhibited the induction of pancreatic carcinoma by BOP, decreasing the incidence of carcinoma to 24 percent compared with an incidence of 75 percent in nondiabetic control animals (p less than 0.002). In diabetic animals, the degree of inhibition of carcinogenesis paralleled the severity of the diabetes. Blocking the diabetogenic effect of streptozotocin with nicotinamide restored the incidence of induced invasive pancreatic carcinoma to that occurring in nondiabetic control animals. In the hamster model, diabetes appears to have a strong influence on susceptibility to the development of pancreatic carcinoma.
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PMID:Influence of diabetes on susceptibility to experimental pancreatic cancer. 296 53

Because epidermal growth factor (EGF) is rapidly bound and internalized into rat pancreas, stimulates uptake of tritiated thymidine, and increases pancreatic weight, a cocarcinogenic effect on pancreatic cancer seemed likely. Pancreatic adenocarcinomas were induced in 70 female Syrian hamsters by 19 weekly s.c. injections of N-nitrosobis(2-oxopropyl)amine (BOP) (10 mg/kg). From Wk 5 through Wk 8 of BOP injections, additional s.c. injections of EGF (5 micrograms every 3 days for 10 injections) were given to 45 animals, while 25 received saline solution. An additional group of 10 received EGF alone, and another 10 animals received saline solution alone (controls). Eleven wk later, the mean body weight of EGF-treated animals increased by 29% as compared with that of controls, and their mean pancreatic weight relative to body weight increased by 44% as compared with controls. The mean body weight of EGF + BOP-treated animals increased by 10%, and their pancreatic weight relative to body weight increased by 22% as compared with that of animals treated with BOP alone. The incidence of pancreatic cancer in the EGF + BOP-treated animals was 75% versus 44% in those treated with BOP alone (P = 0.016). No tumors developed in either animals treated with EGF alone or control animals. EGF augments pancreatic carcinogenesis induced by BOP. The incidence of bronchial carcinomas doubles.
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PMID:Pancreatic cancer in the Syrian hamster induced by N-nitrosobis(2-oxopropyl)-amine: cocarcinogenic effect of epidermal growth factor. 300 3

The effects of a single intragastric application of dibutyltin dichloride (DT), at a dose of 30 mg/kg body weight, on N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic carcinogenesis were studied in female Syrian golden hamsters. DT, which has been shown to selectively induce bile duct injury, was administered either 1 week before or after BOP initiation. BOP was injected subcutaneously once a week for 5 weeks at a dose of 10 mg/kg body weight. Controls were injected with BOP alone or given DT without carcinogen. Animals sacrificed at the end of the 25-week experimental period showed a significant inhibitory effect of DT on pancreatic carcinoma induction when DT was given before BOP treatment, although no such influence was evident with DT treatment following BOP exposure. These results indicate that the bile duct and more especially common bile-duct injury induced by DT may be relevant to the inhibition of the initiation stage of BOP-induced pancreatic carcinoma development in Syrian hamsters.
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PMID:Inhibitory effect of dibutyltin dichloride on pancreatic adenocarcinoma development by N-nitrosobis(2-oxopropyl)amine in the Syrian hamster. 309 18

The rates of uptake of the carcinogen N-nitrosobis(2-oxopropyl)amine (BOP) by hepatocytes isolated from Fischer rats and Syrian hamsters were determined in order to investigate species differences in cellular transport of the carcinogen. Initial rates of uptake of [1-14C]BOP by hepatocytes were measured using a rapid centrifugation technique. At cell densities from 1.5 to 6 x 10(6) cells/ml, initial rates of uptake were as much as 4-fold more rapid in hamster hepatocytes than in those of the rat. The cell/medium distribution ratio for hamster hepatocytes reached a value of 9.0 after a 20-min incubation with an extracellular BOP concentration of 20 microM. Under the same conditions, the cell/medium distribution ratio for rat hepatocytes was only 2.4. These results indicated that BOP uptake proceeded against a concentration gradient and was more rapid in hamster hepatocytes. In both species, the rates of uptake were saturable with increasing concentration (2-685 microM) and displayed biphasic kinetics characteristic of high-affinity (Km less than 20 microM) and low-affinity (Km greater than 30 microM) processes for the uptake of BOP. Evidence for the involvement of an ATP-dependent active carrier-mediated transport process was obtained from experiments in which hepatocytes were preincubated with metabolic inhibitors. Significant inhibition of uptake was observed in the presence of KCN, carbonyl cyanide-3-chlorophenylhydrazone, antimycin A, oligomycin and other agents which interfere with electron transport or ATP generation. Based on the reduction in uptake rates, rat hepatocytes were more sensitive to the effects of these inhibitors. These results suggest that the entry of BOP into hepatocytes is under cellular regulation and that the more rapid rate of uptake in liver cells of the hamster may be one factor responsible for the observation that BOP is a more potent hepatotoxin and carcinogen in this species.
Carcinogenesis 1988 Oct
PMID:Uptake of N-nitrosobis(2-oxopropyl)amine by isolated rat and hamster hepatocytes: species differences and evidence for an active carrier-mediated transport process. 316 56

A rapid-production model incorporating the principle of selection by resistance to cytotoxicity demonstrated earlier for liver carcinogenesis in rats was established for pancreatic carcinoma development in Syrian hamsters. Adenocarcinomas were induced in 84% of treated animals by 10 weeks after initiation with 70 mg of N-nitroso-bis(2-oxopropyl)amine (BOP) per kg of body weight when augmentation pressure (choline-deficient diet combined with DL-ethionine and L-methionine and administration of 20 mg/kg BOP upon return to basal diet) was applied three times. A 52% yield of cholangiocellular tumors also resulted from this experimental protocol.
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PMID:Rapid production of pancreatic carcinoma by initiation with N-nitroso-bis(2-oxopropyl)amine and repeated augmentation pressure in hamsters. 319 71

The expression of blood group-related and tumor-associated antigens was examined in pancreatic adenocarcinomas and in the normal pancreas of hamsters to determine if this expression correlated with the host blood group and/or stage of carcinogenicity, respectively. Pancreatic tumors were induced by 4 weekly treatments of hamsters with N-nitrosobis(2-oxopropyl)amine (BOP) and analyzed immunohistochemically during different stages of tumor progression with polyclonal antibodies (PoAbs) and monoclonal antibodies (MoAbs) against A, B, O and Lewis (Le) isoantigens, including X, Y and CA 19-9 monosialoganglioside (gastrointestinal cancer antigen, GICA), as well as with PoAbs detecting human carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP) and the beta-subunit of human chronic gonadotropin (beta-HCG). The red blood cells of both control and tumor-bearing hamsters expressed AB and Le(a+b+)-like blood group types, as detected by polyvalent antisera. However, none of the MoAbs reacted with the hamster red blood cells. In the pancreas, all PoAbs against blood group antigens reacted with hyperplastic ducts and ductules at very early stages of carcinogenesis, as well as with neoplastic lesions, but not with normal pancreatic cells, except for the acinar cells, which were stained with PoAb-B, PoAb-Lea and PoAb-Leb. None of the MoAbs showed any affinity for the normal pancreatic cells; however, they reacted to various degrees with induced hyperplastic and neoplastic tissue. Reactivities of several MoAbs with malignant cells were greater than those with hyperplastic lesions: MoAb-B was highly reactive with all induced lesions, MoAb-A less reactive, and MoAb-H and MoAb-Ley (which has 6 sugar chains) detected only some cancer cells. Neither of the two MoAb-Lex (with 5 carbohydrate chains) reacted with carcinoma cells, although they did bind to a few hyperplastic cells. Neither MoAb-Lea and MoAb CA 19-9, nor PoAbs against CEA, AFP and beta-HCG, reacted with any normal, hyperplastic or malignant cells. These results demonstrate the differential reactivity of these PoAbs and MoAbs in normal and malignant pancreatic tissue and show that blood group antigens, especially the B isoantigens, are specific markers for induced pancreatic duct tumors in hamsters.
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PMID:Blood-group antigen expression during pancreatic cancer induction in hamsters. 331 27

The activation of N-nitrosobis(2-oxopropyl)amine (BOP) by pancreas acinar and duct tissue from Syrian hamsters and MRC-Wistar rats in vitro and in vivo was measured in terms of the production and repair of DNA damage. Hamsters were given BOP (1 X 10 mg/kg, s.c.). DNA single strand breaks (SSB) were measured over 2 weeks. Significantly more SSB were present in duct than in acinar tissue. Their persistence in the duct fragments was due to a slower rate of repair. In a related experiment, duct fragments were isolated from BOP-treated (1 X 10 mg/kg, s.c.) hamsters 24 h after exposure and cultured for 6 days, or were isolated 7 days after exposure. The extent of DNA damage was comparable in the two groups, indicating that the repair process(es) were still operative in cultured cells. Isolated duct fragments were exposed to either BOP or N-nitrosomethyl(2-oxopropyl)amine (MOP) in vitro. MOP produced significantly more DNA damage than BOP even at a 5-fold lower dose. This is consistent with the greater carcinogenicity of MOP in the pancreas. BOP produced significantly less DNA damage in the rat pancreas than in the hamster pancreas. The rate of repair was at least twice as fast in the rat pancreas as in the hamster pancreas. There did not appear to be any preference for acinar or duct tissue in rats as there was in hamsters. This procedure was validated in rats by the use of the rat pancreas carcinogen azaserine, which only produced DNA damage in rat acinar tissue.
Carcinogenesis 1988 Jun
PMID:The production and repair of DNA damage by N-nitrosobis(2-oxopropyl)amine and azaserine in hamster and rat pancreas acinar and duct cells. 337 Jul 46


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