Jürgen Althoff

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

After a short latency (15 weeks), a 100% incidence of pancreatic neoplasms was induced in Syrian golden hamsters, following the administration of 2,2′‐dihydroxy‐di‐n‐propylnitrosamine (DHPN). Data extracted from reports of human pancreatic neoplasms were compared with findings relative to the induced neoplasms. The latter resembled human pancreatic tumors, in both biological and morphological aspects.

Dibutylnitrosamine Carcinogenesis in Syrian Golden and Chinese Hamsters

Summary Comparative studies with Syrian Golden and Chinese hamsters after intragastric and subcutaneous treatment with dibutylnitrosamine are reported. In both species morphologically similar tumors of the urinary bladder, forestomach, oral, and nasal cavities occurred. Syrian Golden hamsters mainly had tumors of the lower respiratory tract, while the Chinese hamsters developed tumors mainly of the digestive tract. The effect in each case was not dependent on the route of administration.

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.

A chronic study of artificial sweeteners in Syrian golden hamsters.

Chronic administration of saccharin and sodium or calcium cyclamates in drinking water to Syrian golden hamsters, up the maximum tolerated dose level, failed to induce an excess of tumors compared to controls; nor were any urinary bladder tumors found.

Improvement of pancreatic cancer model by modified treatment with N-notrosobis (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.

Urinary bladder neoplasms in Syrian hamsters after administration of N-nitroso-N-methyl-N-dodecylamine

The biological effect of N-nitroso-N-methyl-N-dodecylamine (NMDA) was examined in Syrian hamsters as part of a comparative study. Data obtained show that after intragastric administration of NMDA, the urinary bladder was the main target organ for the carcinogenic effect. Transitional cell neoplasms developed and a positive dose response relationship was observed. Lung tumors occurred only in female hamsters, whereas males more frequently showed neoplasms of the nasal cavity and digestive tract. Die biologische Wirkung von N-Nitroso-N-Methyl-N-Dodecylamin (NMDA) wurde bei Syrischen Hamstern in einer vergleichenden Untersuchung geprüft. Die Ergebnisse zeigten, daß nach intragastrischer Verabreichung von NMDA vorwiegend die Harnblase von der carcinogenen Wirkung betroffen ist. Übergangsepithel-Geschwülste entwickelten sich, und eine positive Dosis Wirkungsbeziehung wurde beobachtet. Lungentumoren entstanden nur bei weiblichen Hamstern, während männliche Tiere häufiger Geschwülste der Nasenhöhle und des Verdauungstraktes zeigten.

Carcinogenic Activity of Aliphatic Nitrosamines Via the Mather's Milk in the Offspring of Syrian Golden Hamsters

Certain nitroso compounds studied in hamsters have been found to cause tumors mainly in the respiratory tract (1). Diethylnitrosamine (DEN) also had a transplacental carcinogenic effect in hamsters (2). When the litters of treated and untreated mothers were exchanged, tumors were found only in the offspring of carcinogen-treated mothers nursed by untreated mothers. The offspring of untreated mothers nursed by mothers treated with carcinogen until the end of pregnancy showed no neoplastic alterations in the respiratory tract (3). We were able to show the presence of nitroso substances in the placenta and fetus of treated pregnant hamsters. Therefore, it was assumed that under these conditions, little or no carcinogen reached the young via the milk after delivery. In the experiments reported here, the effect on the young of carcinogen administered to mothers during lactation was studied. Materials and Methods. In this set of experiments, 6-month-old hamsters were treated with high doses of DEN or dibutylnitrosamine (DBN) 1 to 30 days after delivery. Three groups of five animals received sc administrations of 5, 10, and 20 mg/kg of body weight of DEN dissolved in water. Three other groups received 300, 600, and 1200 mg/kg of body weight of DBN in olive oil (Table I). Results. Nearly one-third of the offspring in the DEN groups died while nursing, showing acute toxic alterations in the liver and kidney. These changes were not observed in the DBN groups or in the controls. The experiments are still underway, with approximately 50% of the young still living more than 1 year after the treatment of their mothers. Focal hyperplastic and dysplastic alterations of the mucosa in the trachea and nasal cavity were seen in treated mothers. All mothers also had tracheal papillary tumors.

Structure of the pancreas in Syrian hamsters

The Syrian hamster is a suitable animal model for the study of pancreatic neoplasms of ductal origin. Therefore, the present study was performed to obtain basic information on the pancreas of this spe

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.

Transplacental effects of nitrosamines in Syrian hamsters: I. Dibutylnitrosamine and nitrosohexamethyleneimine

The transplacental carcinogenic effects of dibutylnitrosamine (DBN) and nitrosohexamethyleneimine (N-6-MI) were examined in Syrian hamsters. A proportion of both substances reached the fetal tissue unaltered. No macroscopic malformations were observed in the offspring; however, postnatal mortality was high. Respiratory tumours were found upon histologie examination of surviving animals. Single doses of 30 mg/kg body weight (b.w.) DBN and 2 doses of 10 mg/kg b.w. N-6-MI did not induce tumours in the P-generation, but led to a low tumour incidence in the F1-generation (DBN, 7.0%; N-6-MI, 2.0%). Treatment for up to eight days during the second half of pregnancy led to a higher tumour incidence in the P-generation (DBN, 22%; N-6-MI, 20%), than in the F1-regeneration (DBN, 6.0%; N-6-MI, 10%). Die transplazentare Wirkung von Dibutylnitrosamin (DBN) and Nitrosohexamethylenimin (N-6-MI) wurde an Syrischen Hamstern untersucht. Beide Substanzen erreichten teilweise unverändert das fetale Gewebe. Bei den Jungen wurden keine makroskopisch nachweisbaren Mißbildungen gefunden. Die postnatale Mortalität war jedoch hoch. Induzierte Tumoren zeigten sich im Respirationstrakt. Einzeldosen von 30 mg DBN/kg KG und 2 Dosen von 10 mg N-6-MI/kg KG erzeugten keine Neoplasmen in der P-Generation, führten aber noch zu einer geringen Tumorrate in der F1-generation (DBN, 7,0%; N-6-MI, 2,0%). Bei Behandlung (bis zu 8 x) während der zweiten Hälfte der Tragzeit war die Häufigkeit der Tumoren in der P-Generation (DBN: 22%, N-6-MI, 20%) höher als in der F1-Generation (DBN, 6,0%, N-6-MI, 10%).