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

The effect of truncal vagotomy (TV) on pancreatic carcinogenesis initiated with N-nitrosobis(2-oxopropyl)amine (BOP) was investigated in 81 female Syrian golden hamsters. The animals were divided into four groups according to the treatment, groups 1 and 2 serving as non-initiated controls receiving a single s.c. injection of 0.9% NaCl followed by either a sham operation or TV respectively, at week 2. Groups 3 and 4 were given a single s.c. injection of 70 mg/kg body wt of BOP before the sham operation or TV. All hamsters were killed at week 24, and the pancreas, liver and gall bladder tissues were examined histologically. While TV itself caused no significant change in pancreatic weight, the incidence of pancreatic carcinomas in hamsters from group 4 was 48.4%, significantly higher than the 16.7% evident in hamsters from group 3 (P less than 0.05). GLC analysis of the bile acid composition of gall bladder bile from hamsters not receiving carcinogen 1 and 4 months after TV revealed significantly decreased secondary bile acids. The results thus indicated that changes in bile acid composition may be involved in enhancement of BOP-initiated pancreatic carcinogenesis in hamsters by TV.
Carcinogenesis 1991 Jul
PMID:Promoting effect of truncal vagotomy on pancreatic carcinogenesis initiated with N-nitrosobis(2-oxopropyl)amine in Syrian golden hamsters. 207 Apr 87

The modifying effects of the phenolic antioxidant catechol (CC) and its analogs hydroquinone (HQ) and resorcinol (RN) on pancreatic carcinogenesis were evaluated in 146 female Syrian golden hamsters. Groups of animals received either saline or 70 mg/kg body wt N-nitrosobis(2-oxopropyl)amine (BOP) s.c. injections, twice with a 2 week interval, followed by basal diet or diet containing 1.5% of CC, HQ or RN, and 0.75% CC from week 4. All hamsters were killed at week 20 and histopathologically examined for development of pancreatic, liver and gall bladder lesions. The total numbers of pancreatic lesions comprising carcinomas, atypical ductal hyperplasias and ductal hyperplasias per hamster were significantly decreased in animals receiving BOP followed by CC, HQ and RN when compared to those in hamsters given BOP followed by basal diet. Incidence values for atypical ductal hyperplasias were also significantly decreased by the RN or 0.75% CC treatments. The results thus suggest that pancreatic carcinogenesis initiated by BOP in Syrian hamsters can be inhibited by treatments with phenolic antioxidants such as CC, HQ and RN for a relatively short experimental period.
Carcinogenesis 1991 Jul
PMID:Effects of catechol and its analogs on pancreatic carcinogenesis initiated by N-nitrosobis(2-oxopropyl)amine in Syrian hamsters. 207 May

The metabolism of the pancreatic carcinogen N-nitroso-bis(2-oxopropyl)amine (BOP) was studied using primary hepatocytes and acinar and duct cells isolated from Syrian hamsters. Metabolic activation of BOP was verified by detecting its conversion to CO2 covalently bound metabolites and soluble products containing the alpha-carbon of the nitrosamine. At concentrations below 0.2 mM, BOP was completely activated by hepatocytes within 60 min. At high substrate concentration (1 mM) or high cell density (5 x 10(6) cells/ml), reduction of BOP to N-nitroso(2-hydroxypropyl) (2-oxopropyl)amine and N-nitrosobis(2-hydroxypropyl)amine contributed significantly to the metabolic profile. The conditions which favored metabolic activation of BOP were used to compare metabolism by hepatocytes and pancreatic cells. Under such conditions, the ratio of activation products formed by hepatocytes versus those formed by acinar cells was 14.5:1; the corresponding ratio for covalently bound metabolites was 19:1. Hepatocytes activated BOP 106 times more rapidly than duct cells as determined from yields of activation products or 152 times more rapidly as determined from labeling of cellular macromolecules. Acinar cells showed a higher capacity for metabolic activation than duct cells. The ratio for the yield of activation products from acinar versus duct cells was 4.3:1; the corresponding ratio for covalent binding was 5.8:1. The relatively low capacity of pancreatic cells for activation of BOP compared to hepatocytes is in agreement with the low levels of DNA binding in the pancreas compared to other organs after administration of BOP to the hamster in vivo. The observation that the ratio for total covalent binding of BOP in hepatocytes versus acinar cells was higher than that seen previously for the liver versus the pancreas in vivo is consistent with the hypothesis that alkylating agents derived from BOP reach the pancreas after formation in other organs. The liver would be the prime source for such alkylating agents.
Carcinogenesis 1990 Apr
PMID:Metabolism and activation of the pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine by isolated hepatocytes and pancreatic cells of the Syrian hamster. 210 19

Cholecystokinin (CCK) has been shown to promote pancreatic growth and azaserine-induced pancreatic carcinogenesis in rats. The present study was carried out to determine effects of CCK on pancreatic growth and carcinogenesis in the N-nitrosobis(2-oxopropyl)amine (BOP) hamster model. One hundred male Syrian golden hamsters were injected s.c. once weekly with 20 mg BOP/kg body wt at 6, 7 and 8 weeks of age, and divided into four groups of 25 animals each, which received one of the following treatments (once daily, 3 days/week for 16 weeks): gelatin; CR-1409, a potent CCK-receptor antagonist; CCK-8, 2.5 micrograms/kg body wt; or CCK-8 in combination with CR-1409 (30 min before CCK treatment). The animals were killed after 19 weeks. The growth of the pancreas but not the incidence of pancreatic (pre)neoplastic lesions was enhanced by CCK-8. CR-1409 did not influence the effect of CCK on pancreatic growth.
Carcinogenesis 1990 Dec
PMID:Role of cholecystokinin in the development of BOP-induced pancreatic lesions in hamsters. 226 73

The effects of prostaglandin synthesis inhibitors on development of N-nitrosobis(2-oxopropyl)amine (BOP)-initiated pancreatic tumors were investigated. Female Syrian golden hamsters were given five weekly s.c. injections of BOP (10 mg/kg body weight) during the first 5 weeks and then given 20 p.p.m. indomethacin in the drinking water, 0.25% phenylbutazone in the diet, 1% aspirin in the diet, or no treatment (control group). The resultant incidence of pancreatic carcinoma at week 32 was significantly lower (P less than 0.05) in animals receiving phenylbutazone (36.8%) than in the controls (71.4%) and the numbers of carcinomas per hamster were significantly reduced by indomethacin (0.63) and phenylbutazone (0.58) treatment compared with the control group value (1.29). Aspirin also showed a tendency to decrease pancreatic tumor incidence, but this was not significant. Thus, prostaglandin synthesis inhibitors reduce the development of pancreatic cancer when administered during the post-initiation phase in this animal model.
Carcinogenesis 1990 Mar
PMID:Effects of various prostaglandin synthesis inhibitors on pancreatic carcinogenesis in hamsters after initiation with N-nitrosobis(2-oxopropyl)amine. 231 Nov 81

The persistence of 7- and O6-alkylation of guanine in DNA of cell nuclei of male Syrian hamster pancreas, liver, kidneys, lungs [target tissues of N-nitrosobis(2-oxopropyl)amine (BOP)] and salivary glands (nontarget tissue) was studied immunocytochemically 6 h, 1, 3, 7, 14, 28, and 56 days after a single s.c. injection of 20 mg BOP/kg. Conventional antisera raised against O6-methylguanine and imidazole-ring-opened 7-methyl-guanine were used. Persistent alkyl-specific staining was observed for up to 7 days (7-alkylguanine) or 56 days (O6-alkylguanine) in inter- and intralobular duct cells and centro-acinar cells of the pancreas, periportal hepatocytes and bile duct cells of the liver, cells of the proximal convoluted tubules of the renal cortex, and bronchiolar Clara and alveolar cells in the lungs. Both adducts disappeared from centrilobular liver cells within 1 day, from pancreatic acinar cells within 3 days, and from ducts and acini of the submandibular salivary glands within 14 days after BOP treatment. A high level of persistent O6-alkylation of guanine was related with a high tumor incidence only in case of the ductal/ductular system of the pancreas, the main target tissue of BOP-induced carcinogenesis. The relatively weak carcinogenicity of BOP in other tissues with long-term persistence of O6-alkylguanine in DNA indicates that the formation and persistence of DNA alkylation are not sufficient to account for the carcinogenic organotropism of BOP. Additional factors, such as cell proliferation, appropriate promoting stimuli and the (onco)genes critically involved, may be as important as the modification of DNA.
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PMID:Long-term persistence of DNA alkylation in hamster tissues after N-nitrosobis(2-oxopropyl)amine. 232 57

We previously reported an enhancement of pancreatic carcinogenesis induced by N-nitrosobis(2-oxopropyl)amine (BOP) in hamsters fed diets containing high levels of corn oil. The research presented here compared diets high in corn oil with those high in beef tallow in the enhancement of pancreatic carcinogenesis. Pancreatic cancer was induced with 20 mg BOP/kg body wt, s.c. administered at 8 weeks of age. One week later, hamsters were assigned to one of five diet treatments: (i) 4.3% corn oil (control); (ii) 20.5% corn oil (high corn oil); (iii) 0.5% corn oil + 3.8% beef tallow (low beef tallow); (iv) 0.6% corn oil + 19.9% beef tallow (high beef tallow); and (v) 5.1% corn oil + 15.4% beef tallow (high fat mixture). These diets were fed until the study ended 84 weeks after BOP treatment. Hamsters were trained through pair feeding to consume the same calorie allotment as the control corn oil group. By the end of the experiment, BOP-treated hamsters that were fed diets containing beef tallow were consistently heavier than those fed corn oil. Survival was longer in hamsters fed the high-beef tallow and high-fat mixture compared with the other diet groups. Tumor data were age adjusted to correct for survival differences. Pancreatic adenoma incidence and multiplicity (no./effective animal) were higher in hamsters fed beef tallow than those fed corn oil diets. Carcinoma in situ multiplicity was elevated in hamsters fed high-fat diets irrespective of the nature of fat fed. Pancreatic adenocarcinoma multiplicity was elevated in hamsters fed the low- or high-beef tallow diets compared with the low- or high-corn oil diets. The mixture of fat resulted in an intermediate yield.
Carcinogenesis 1990 May
PMID:Comparison of the effects of dietary beef tallow and corn oil on pancreatic carcinogenesis in the hamster model. 233 5

The effect of selenium intake on the development of pancreatic cancer was investigated in female Syrian golden hamsters. Four-week-old hamsters were divided into 2 groups according to the selenium level in their drinking water and were fed a purified diet containing less than 0.05 ppm selenium. Starting 4 weeks later, groups received 10 s.c. injections at weekly intervals of N'-nitrosobis(2-oxopropyl)amine (BOP) dissolved in saline, while controls received saline alone. When the animals were killed 18 weeks after the last injection, palpable tumors were less frequent in the high-selenium group than in animals receiving low-selenium supplement, the numbers of histologically diagnosed cancerous lesions also being significantly reduced by high selenium intake. The selenium level and glutathione peroxidase activity in serum and pancreas were significantly greater in the high-selenium group. Moreover, selenium levels and glutathione peroxidase activity were both significantly higher in tumor-bearing tissue. The results suggest that glutathione peroxidase is involved as an intermediate factor in prevention of carcinogenesis by selenium.
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PMID:Inhibitory effect of selenium on hamster pancreatic cancer induction by N'-nitrosobis(2-oxopropyl)amine. 236 2

Pancreatic carcinoma induced in the Syrian hamster by the carcinogen N-nitrosobis(2-oxopropyl)amine (BOP) is of interest because of the ductal/ductular morphology of the tumors, which resembles human pancreatic cancer. However, whether hamster tumors arise from pre-existing ductal epithelium or from acinar cells has not yet been determined. The present study shows that a monoclonal antiserum to cytokeratin (an epithelial marker), when applied to normal hamster pancreas sections, stained centroacinar, ductular and ductal epithelium but did not stain acinar cells. We therefore examined pancreatic tissue from hamsters with benign and malignant neoplasms induced by BOP. The antiserum strongly stained the cells of all BOP-induced lesions (cysts, pseudoductules, hyperplasia, dysplasia and carcinomas). No acinar cell staining was observed in BOP-treated pancreas. These findings support the hypothesis that BOP-induced neoplasms arise from ductal epithelium and not from acinar cells.
Carcinogenesis 1987 Oct
PMID:Cytokeratin antigen in BOP-induced pancreatic tumors--implications for histogenesis. 244 64

Levels of amylase isozymes in the urine and serum of Syrian hamsters during pancreatic carcinogenesis, induced by N-nitrosobis(2-oxopropyl)amine (BOP), were investigated. BOP was injected subcutaneously (sc) into female Syrian golden hamsters at a dose of 10mg/kg once weekly for 6 wk and amylase activities in urine and serum samples were measured every other week from the first treatment of BOP. Although total amylase in the urine showed no remarkable changes, the pancreatic type isozyme demonstrated only very low levels for the first 6 wk and then from wk 8, became elevated showing continuously high levels in all animals thereafter. Animals were sacrificed at wk 10, 14, and 18. Dysplastic lesions of the pancreas developed in all the hamsters investigated. Furthermore, pancreatic adenocarcinomas were also observed in all animals sacrificed at wk 18. Thus, the results suggest that measurement of pancreatic isoamylase in the urine might allow early indication of pancreatic tumor development in hamsters.
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PMID:Elevated activity of pancreatic type amylase in the urine as an early indicator of pancreatic tumors in hamsters. 247 47


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