Biomedical subjects

P Pour

Publications and source records attributed to P Pour.

At least 55 records · Page 3Linked to original sources

PubMed1978

Metabolism of the pancreatic carcinogen N-nitroso-bis(2-oxopropyl)amine after oral and intraperitoneal administration to Syrian golden hamsters.

The levels of N-nitroso-bis(2-oxopropyl)amine (BOP) and its metabolites in the urine, blood, bile, and pancreatic juice were compared after ip and oral administration of BOP to Syrian golden hamsters to explain the differing organotropic tumor spectra resulting from treatment by these two routes. The levels of BOP and its metabolites N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) and N-nitroso-bis(2-hydroxypropyl)amine in the urine, blood, bile, and pancreatic juice were generally less after oral administration than after ip administration. The results suggested that HPOP may be a proximate pancreatic carcinogen in hamsters administered BOP, inasmuch as it was the major metabolite in the blood and pancreatic juice after ip administration. However, the results did not indicate a mechanism for the increased incidence of bile duct tumors that after oral administration of BOP.

Administration, Oral↗

PubMed1978

Islet cells as a component of pancreatic ductal neoplasms. I. Experimental study: ductular cells, including islet cell precursors, as primary progenitor cells of tumors.

The ductular complex of the Syrian hamster pancreas represents a system of conduit which encompasses intercalated (intralobular), periinsular, and intrainsular ductules. The intercalated (intralobular) ductules comprise centroacinar and intercalated cells. A meshwork of small ductules (invisible by usual histologic procedures) surrounds islets (periinsular ductules) and extends in the form of often ramified tiny channels within the islet (intrainsular ductules). Although the function of the latter ductules is obscure, their cells seem to make up one of the undifferentiated cellular units of the pancreas, and as such are also the progenitors of beta-cells of the islets (islet cell precursor = IP). Systematic histologic examination of the pancreas in this species treated with pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine indicated that ductular cells, especially those of periinsular and intrainsular origin, are the most responsive to this carcinogen. The neoplastic process was initiated with hyperplasia of intercalated (intralobular) ductular and interlobular ductal cells associated with newly formed islets (nesidioblastosis). This process was followed by excess formation of mature but especially of immature islet cells and their precursors (IP) in the islet periphery, as well as with the appearance, distention, and multiplication of periinsular and particularly of intrainsular ductules. The hyperplasia, metaplasia, and malignant alteration of these periinsular and intrainsular ductules (including IP) and, to a lesser degree, of intercalated ductules indicated their histogenetic relationship and their potency for reproducing embryonic tissue on carcinogenic stimulus. The similarity of some induced lesions to diabetes has been emphasized.

Animals↗

PubMed1978

The results of pancreatography during pancreatic carcinogenesis.

Systematic histologic-pancreatographic examination of the pancreas during pancreatic ductal carcinogenesis revealed both specific and nonspecific diagnostic criteria. Ductal changes due to hyperplasia of ductal epithelium were recognized as distention rather than narrowing. This condition, however, occurred in limited numbers during advanced ductal alteration and was found to be an insignificant criterion. The most reliable tumor marker was complete ductal obstruction: ductal deterioration (displacement, deformity) occurred in 63% of the tumor cases, a pooling effect occurred in 44%, and a filling defect occurred in 42%. In both histologic and pancreatographic studies was found the "chain of lakes" caused by ductular proliferation or adenomas both of which seem to represent precursor stages of adenocarcinomas. Some neoplasms escaped diagnosis, due to either their small size, anatomic location, or specific histologic patterns. The data indicated that pancreatography per se as an early detection tool is unreliable.

Adenocarcinoma↗

PubMed1978

Effect of cholecystoduodenostomy and choledochostomy in pancreatic carcinogenesis.

The pancreatic carcinogen N-nitrosobis(2-oxopropyl)-amine was administered to Syrian golden hamsters after cholecystoduodenostomy and choledochostomy to investigate a possible bile reflux mechanism as a factor in pancreatic carcinogenesis. The induced lesions were similar in morphology, multiplicity, and distribution to those of animals in other studies without surgery. Hence the findings contraindicate the importance of biliary reflux in pancreatic tumor induction. Other possible mechanisms are discussed.

Adenocarcinoma↗

PubMed1977

Transplacental effect of nitrosamines in Syrian hamsters. IV. Metabolites of dipropyl- and dibutylnitrosamine.

The present investigations showed that assumed and established metabolites of dipropylnitrosamine and dibutylnitrosamine reach the Syrian hamster fetus after subcutaneous (s.c.) treatment of their mothers (at day 14 of gestation). The compounds [2-hydroxypropylpropylnitrosamine, HPPN; 2-oxopropylpropylnitrosamine, OPPN; methylpropylnitrosamine, MPN; N-nitrosobis(2-hydroxypropyl)amine, BHP; and 4-hydroxybutylbutylnitrosamine, HBBN] were still present in the examined tissue (maternal blood, placenta, fetus, amniotic fluid) 4--6 h after s.c. injection. The overall incidence of transplacentally induced tumors was lower in the F1- than in the P-generation and comparatively longer latencies were also observed in the F1- generation. However, in some groups low incidences were found of tumors which did not occur in the mothers (i.e., nasal cavities: BHP, HBBN; trachea: HBBN; lungs: HPPN, BHP, HBBN; liver: OPN, MPN, BHP, HBBN). Compared to exposure at early gestation, the transplacental carcinogenic effect increased at day 14 of gestation. Neoplasms originating in other organs were not associated with a transplacental effect of the examined nitrosamines.

Amniotic Fluid↗

PubMed1977

Local and systemic effects of 1-acetoxypropylpropylnitrosamine in Syrian golden hamsters.

1-Acetoxypropylpropylnitrosamine (1-APPN) was synthesized and its biological effect examined in Syrian hamsters after subcutaneous (s.c.) administration. 1-APPN induced mesenchymal and epithelial neoplasms at the injection sites, as well as epithelial tumors in remote organs. Local neoplasms were a.c. sarcomas, mammary adenocarcinomas and Schwannomas, whereas tumors of the respiratory tract (papillary polyps, papillomas, adenomas, epidermoid carcinomas, and adenocarcinomas) were attributed to a systemic effect as were pancreas duct tumors. Neoplasms which originated in the upper digestive and genital tracts of females (papillomas, epidermoid carcinomas) may be related to a systemic and local effect of 1-APPN.

Animals↗

PubMed1977

Comparison of the effect of beta-oxidized dipropylnitrosamine metabolites administered at equimolar doses to Syrian hamsters.

After subcutaneous administration of dipropylnitrosamine (DPN) to Syrian hamsters, gas-liquid chromatographic analysis of the 16-h urine revealed the DPN metabolites, 2-hydroxypropyl-, 2-oxopropyl-, and methylpropylnitrosamines. In a related series of experiments, hamsters received equimolar doses of the above compounds and of N-nitrosobis(2-hydroxypropyl)-amine (BHP) and 2,2'-dimethyldipropylnitrosamine (DMDPN). The metabolites as well as BHP and DMDPN had a weaker effect than did DPN on the rate and/or latency of respiratory tumors. In the respiratory tract, the segmental tumor distribution and histological types varied according to the compounds. The metabolites of DPN induced additional tumors in the digestive tract. These experiments do not support the concept that the beta-oxidized metabolites of DPN are the proximate carcinogens of the parent compound.

Animals↗

PubMed1977

Transplacental effects of nitrosamines in Syrian hamsters. II. Nitrosopiperidine.

Nitrosopiperidine (NP) was found in Syrian hamsters quantitatively in the maternal blood for more than 8 h after subcutaneous injection, whereas it disappeared from placenta, fetus and amniotic fluid within the same time period. For N6MI, only traces were seen after 2 h in the same tissues. The long-term transplacental effect of a single dose of NP was weak, as demonstrated by a low respiratory tract tumor incidence (P-generation: 54%, F1- generation: 4%). Some tumors occurring in the digestive tract of exposed young were not found in their mothers and not commonly observed in controls. These tumors were considered a borderline transplacental effect. Tumors of other sites (i.e., the urogenital and genital tracts, reticuloendothelial system, endocrine organs and other tissues) corresponded in incidences to the overall fluctuations observed in this hamster colony.

Animals↗

PubMed1977

Transplacental effects of nitrosamines in Syrian hamsters. III. Dimethyl- and dipropylnitrosamine.

The aliphatic nitrosamines dimethylnitrosamine (DMN), diethylnitrosamine (DEN), dipropylnitrosamine (DPN), and dibutylnitrosamine (DBN) reached fetal tissue in quantitatively measurable amounts after subcutaneous administration to pregnant Syrian hamsters. The compounds were present for at least 2 h in maternal blood, placenta, fetus, and amniotic fluid; DBN was still measurable after 6 h. Only a weak or borderline transplacental effect was seen when incidences and latencies of neoplasms in the respiratory and digestive tracts of the F1-generation were compared with those of the P-generation after exposure to a single dose of DMN or DPN. However, some tumor types occurred at relatively high rates in the young, but were seen only occcasionally in their mothers or in this hamster colony in general.

Amniotic Fluid↗

PubMed1977

The effect of N-nitrosobis(2-oxopropyl)amine after oral administration to hamsters.

Oral administration of N-nitrosobis(2-oxopropyl)amine (BOP) in drinking water to Syrian golden hamsters for 90 days resulted in a high incidence of intra- and extrahepatic bile duct neoplasms. Only a few pancreatic neoplasms and no lung and kidney tumors developed, in contrast to results obtained after subcutaneous BOP administration.

Adenoma, Bile Duct↗

PubMed1977

Improvement of pancreatic cancer model by modified treatment with N-nitroso-bis (2-oxopropyl) amine.

Comparative studies were conducted in 2 groups of Syrian golden hamsters treated with N-nitroso-bis (2-oxopropyl)amine (BOP) weekly for life (group A) or weekly for 6 weeks (group B), and sacrificed at 2-week intervals. Pancreatic neoplasms developed as early as 8 weeks (group B) and 10 weeks (group A); however, in group B there were fewer, smaller lesions, well-differentiated morphologically. Liver neoplasms occurred only in group A, while gallbladder and kidney tumors were seen in both groups. A lower incidence of pulmonary adenomas was found in group B than in group A, which also had pulmonary carcinomas. The results indicate a further advance in the development of a pancreatic cancer model.

Adenocarcinoma↗

PubMed1977

Induction of epithelial neoplasms by local application of N-nitrosobis(2-hydroxypropyl)amine and N-nitrosobis(2-acetoxypropyl)amine.

The local carcinogenic effect of N-nitrosobis(2-hydroxypropyl)amine (BHP) and N-nitrosobis(2-acetoxypropyl)amine (BAP) in Syrian golden hamsters was elucidated by weekly application to the cheek pouch, lip and vaginal epithelium. The tumor type and incidence in BHP- and BAP-treated hamsters, respectively, was as follows: trichoepitheliomas of the lip, 80 and 90%; cheek pouch papillomas, 10 and 0%, and vaginal papillomas, 80 and 70%. Other lesions were recorded in the perineum, rectum and external urethral ostium and could have been due to a local effect of these nitrosamines. In addition, internal organ tumors were observed with each compound and were possibly caused by absorption of the carcinogens.

Animals↗

PubMed1977

Carcinogenic effects of diisopropanolinitrosamine in Sprague-Dawley rats.

The carcinogenic effects of diisopropanolinitrosamine (DIPN) were tested in Sprague-Dawley rats and were then compared with results produced earlier by the same substance in Syrian hamsters. In addition to the similarities, several differences were noted; for example, DIPN caused pancreatic tumors in all the hamsters, but only 1 pancreatic tumor was observed among the 150 rats. Administration of DIPN to rats led to the development of neoplasms in the nasal and paranasal cavities, lungs, thyroid gland, esophagus, liver, and kidneys. The highest tumor incidence in rats was in the nasal cavities. Almost all the pulmonary neoplasms were malignant and were usually squamous cell carcinomas. We found a 15.4-50% incidence of malignant tumors of the thyroid gland; we also noted that thyroid neoplasms occurred at almost the same rate (36.4-50%) in the groups given 1/5, 1/10, and 1/20 the median lethal dose.

Adenocarcinoma↗

PubMed1977

Vinylethylnitrosamine: a potent respiratory carcinogen in Syrian hamsters.

Vinylethylnitrosamine (VEN), an alpha-beta unsaturated analogue of diethylnitrosamine (DEN), which may be formed by the enzymic conversion necessary for carcinogenesis, was synthesized and its biologic effect was examined by sc administration to Syrian hamsters. Distribution studies showed that the maximum amount of unaltered compound was found in various tissues 45 minutes after injection. The chemical was only partially excreted unchanged after 5 hours. Weekly treatment for life resulted in high incidence of malignant respiratory tract neoplasms with short latencies and in tumors of the upper digestive tract and pancreas. The effects of VEN were compared to those of the assumed parent compound, DEN.

Animals↗

PubMed1977

A potent pancreatic carcinogen in Syrian hamsters: N-nitrosobis(2-oxopropyl)amine.

N-Nitrosobis(2-oxopropyl)amine (BOP), a further postulated beta-metabolite of di-n-propylnitrosamine, induced a high incidence of pancreatic duct adenomas and adenocarcinomas as early as 13 weeks in Syrian hamsters receiving weekly sc injections for life and a few pancreatic adenomas, after 28 weeks, in those given a single sc dose. Compared to related compounds, N-nitrosobis(2-hydroxypropyl)amine and N-nitrosobis(2-acetoxy-propyl)amine which are also pancreatic carcinogens, BOP induced only a few neoplasms of the lung, liver, and kidney and none in the nasal cavity, larynx, and trachea. The results therefore indicate progress in developing a more specific model for pancreatic carcinogenesis studies.

Adenocarcinoma↗

PubMed1977

Early lesions of pancreatic ductal carcinoma in the hamster model.

Syrian golden hamsters were treated weekly with 10 mg/kg body weight N-nitrosobis (2-oxopropyl) amine for life (Group 1) or 6 weeks and were sacrificed at biweekly intervals from 2 weeks (Group 1) and 8 weeks (Group 2) after initiation of the experiment. The pancreas was examined in step sections, and the sequential alterations noted for each interval were recorded. Lesions were found in intrapancreatic and extrapancreatic ducts. Equivalent alterations consisting of hyperplasia, metaplasia, atypia, and lesions characteristic of carcinoma in situ developed ubiquitously and simultaneously in pancreatic ducts of different sizes and in ductules, but not in acinar cells. Among the most significant findings were intrainsular ductular formations, their proliferation, and sequential malignant alteration comparable to the involved preexisting ductules. Differences between the two experimental groups were of a quantitative rather than qualitative nature. The incidence and multiplicity of neoplastic lesions at each interval according to group, sex, and anatomic locations of adenocarcinomas are outlined. Predilected areas for some lesions were found. Results indicate a common origin of all induced tumors from a pluripotent cell populating the pancreatic ductal system.

Animals↗

PubMed1977

The pancreas of the Syrian hamster (Mesocricetus auratus). I Anatomical study.

An anatomical study was made of the pancreas of the Syrian hamster (Mestocricetus auratus). The pancreas was found to consist of a head and three well-defined segments: the duodenal, gastric, and splenic lobes. The duct systems from each of the three lobes converge at the head region of the pancreas and develop into two major ducts which enter the distal portion of the common bile duct to form a common duct. The tails of the gastric and splenic lobes are connected by a string of omental fat which contains the major blood vessels of the two lobes. The gross anatomy of the hamster pancreas differs to some extent from that of the mouse and rat, but the principal structure of the ducts is similar.

Animals↗

PubMed1977

Sequential alteration of the pancreas during carcinogenesis in Syrian hamsters by N-nitrosobis(2-oxopropyl)amine.

A systematic histological-pancreatographic study indicated that, during pancreatic carcinogenesis by N-nitrosobis(2-oxopropyl)amine, the ductular cells (cells of intercalated or intralobular ductules and especially those of peri-and intrainsular ductules) are most responsive. The initial proliferation (multiplication) and distension of ductules seemed due to primary hyperplasia of ductular cells, followed by metaplasia, atypia, and malignant alteration. Among 75 induced adenocarcinomas, most were of ductular origin, whereas only a few seemed to arise from ductal epithelium (interlobular, secondary, and main ducts). There was no preferential segment for tumor development. However, about one-third of the adenocarcinomas in the head of the pancreas had a periampullary location, while most neoplasms in other pancreatic lobes arose along the main pancreatic ducts. There was evidence of "leaking" of pancreatic juice through altered epithelium of main ducts, and this may have caused a marked periductal chronic inflammatory reaction.

Adenocarcinoma↗