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Biomedical subjects

J Althoff

Publications and source records attributed to J Althoff.

At least 109 records · Page 6Linked to original sources

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↗

Diallylnitrosamine: a potent respiratory carcinogen in Syrian golden hamsters: brief communication.

Diallylnitrosamine (DAN), one of the few nitrosamines tested thus far that has not induced neoplasms in rats, caused a high incidence of respiratory tract tumors in Syrian golden hamsters treated sc with single or weekly doses of the compound. The effect was dose-dependent. The nasal cavity, larynx, and trachea were the most affected by DAN; most drug-induced tumors at those sites were adenocarcinomas and papillary polyps.

Animals↗

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↗

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↗

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↗

Comparative studies of neoplastic response to a single dose of nitroso compounds. 5. The effect of dimethylnitrosamine in Swiss, ASW/SN and A-strain mice.

The tumorigenic effect of dimethylnitrosamine given once at 5 different dose levels was compared in adult Swiss, ASW/SN and A-strain mice. Considering the overall tumour incidence, at the highest dose level an increase was found in Swiss and ASW/SN mice, but not in A-strain animals. However, the effect of treatment was unequivocal for lung neoplasms. The rate of carcinomas rose significantly in all 3 strains, although a clear dose response-relationship could be established only in Swiss and ASW/SN mice. A dose-dependent effect for adenomas was found solely in Swiss mice.

Adenoma↗

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 histologic 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-generation (DBN, 6.0%; N-6-MI, 10%).

Animals↗

Histogenesis of tumors from the nasal cavities induced by diethylnitrosamine.

Chronic subcutaneous (s.c.) or single intravenous (i.v.) injections of diethylnitrosamine (DEN) to gerbils (Meriones unguiculatus) led to the induction of carcinomas of the nasal cavities in a high incidence. These neoplasms were multifocal in origin, frequently showing mixed cellular patterns of the following cell types: large cuboidal cells, nonciliated columnar cells, ciliated columnar cells, small cells, and squamous epithelial cells. No sensory cells of the olfactory mucosa or neurofibrillar differentiations were found in these neoplasms, although several showed rosette- and pseudorosette-like formations. Dose and route of administration seemed to influence the site of origin and the patterns of cellularity of these tumors. Whereas chronic s.c. injections resulted in carcinomas of the olfactory region, being mostly composed of large cuboidal cells, single i.v. injections led to the development of carcinomas mainly originating from the respiratory-olfactory mucosal junction and composed preferentially of nonciliated and ciliated columnar cells.

Adenocarcinoma↗

A further pancreatic carcinogen in Syrian golden hamsters: N-nitroso-bis(2-acetoxypropyl)amine.

Weekly subcutaneous injection of N-nitroso-bis(2-acetoxypropyl)amine (BAP) for 20 weeks to Syrian golden hamsters induced pancreatic neoplasms in 50% of the animals, as early as 15 weeks from the start of treatment. The carcinogenic potency and organotropic spectrum of BAP were similar to those of N-nitroso-bis(2-hydroxypropyl)amine (BHP). Metabolism studies indicated that BAP was readily converted in vivo to BHP and that BHP was also the major urinary metabolite.

Animals↗

Spontaneous tumors and common diseases in two colonies of Syrian hamsters. I. Incidence and sites.

Syrian hamsters from two colonies [Eppley colony (EC); Hannover colony (HC)] were examined for spontaneous neoplastic and noneoplastic diseases. Significant differences were found in tumor incidence (30%, EC' 42%, HC), occurrence of malignant neoplasms (15%, EC; 32%, HC), appearance of multiple primary tumors in different organs (42%, EC; 30%, HC), average survival rates of tumor-bearing animals, organ distribution and histologic types, and average survival rates of all animals. The frequencies of nonneoplastic diseases also varied between the two colonies. The findings indicated a need for precise histologic evaluation to generate information for comparative purposes regarding the use of hamsters in experimental pathology and carcinogenesis studies.

Animals↗

Spontaneous tumors and common diseases in two colonies of Syrian hamsters. II. Respiratory tract and digestive system.

Spontaneous respiratory tract neoplasms in Syrian hamsters occurred in almost equal frequencies in two colonies: 3% in the Eppley Colony (EC) and 3.6% in the Hannover Colony (HC). Neoplasms were in the nasal cavity, trachea, and lungs, and most were benign; however, 2 adenocarcinomas of the nasal cavity (EC) and 1 adenocarcinoma of the larynx (HC) were found. The incidence of digestive tract tumors showed a more marked difference than that of the respiratory tract: 7% in the EC and 23% in the HC. Digestive tract tumors accounted for 15 and 41% of all tumors in the EC and HC, respectively. All EC digestive tract neoplasms were benign and occurred mostly in males; 19 (83%) were forestomach papillomas and the remaining 4 )17%) were liver hemangioendotheliomas (2) and pancreatic duct adenomas (2). In the HC, almost 50% of the digestive tract neoplasms were malignant and most frequent in females. These tumours include 19(42%) intestinal adenocarcinomas, 18(40%) liver neoplasms (hemangioendotheliomas, cholangiomas, cholangiocarcinomas), 5 (13%) forestomach papillomas, and 2 (4%) gallbladder polyps. The morphology of these neoplasms was reported.

Adenocarcinoma↗

Spontaneous tumors and common diseases in two colonies of Syrian hamsters. III. Urogenital system and endocrine glands.

The frequency of spontaneously occuring neoplasms in the urogenital system and endocrine organs was examined in two Syrian hamster colonies [Eppley colony (EC); Hannover colony (HC)]. With the exception of a renal adenoma in an EC female, the urinary systems of animals in both colonies were free of neoplastic growths. A single epididymal adenoma of the male fenital system (EC) was found. However, incidences of female genital tract tumors were 10 (EC) and 3.5% (HC) and accounted for 34 and 11%, respectively, of all tumors in females. Among all genital tract tumors, 3 (EC) and 57% (HC) were ovarian, 14% (HC) were in the fallopian tubes, 81 (EC) AND 29% (HC) were uterine, and 16% (EC), vaginal. The overall incidence of endocrine organ tumors was similar in both colonies (EC, 22%; HC, 19%). The distribution of these tumors was as follows: pituitary gland; EC, 3%, HC, 0; thyroid gland: EC, 28%, HC, 31%; parathyroid gland: EC,11%, HC, 18%; adrenal cortex: EC, 42%, HC, 31%; adrenal medulla: EC, 7%, HC, 0; and endocrine pancreas: EC, 10%, HC, 31%. The morphology of these neoplasms is described and the incidence compared with those reported in other colonies.

Adrenal Gland Neoplasms↗

N-nitroso-bis(2-acetoxypropyl)amine as a further pancreatic carcinogen in Syrian golden hamsters.

N-Nitroso-bis(2-acetoxypropyl)amine, a possible beta metabolite of N-nitroso-di-n-propylamine, was shown to be a potent carcinogen in the Syrian golden hamster. After a single s.c. treatment, the pancreas was the most affected organ, followed by the liver, respiratory tract, and kidneys. However, repeated application resulted in a higher incidence of neoplasms of the respiratory tract than of the pancreas and kidneys. The effect of N-nitroso-bis(2-acetoxypropyl)amine on toxicity, target tissues, and carcinogenicity was similar to that of N-nitroso-bis(2-hydroxypropyl)amine. The assumption that these two compounds may have similar metabolic pathways was confirmed; N-nitroso-bis(2-acetoxypropyl)amine was readily deesterified to N-nitroso-bis(2-hydroxypropyl)amine in vivo and in vitro.

Animals↗

The ultrastructure of oncolytic spores found on pig skin.

A new type of clostridium spore, derived from melanotic hamster tumors treated with pig skin extracts, was examined in a lyophylized form by electron microscopy (EM). Scanning EM indicated that two out of five preparations contained only spores. The spores exhibited oval forms (1.5 X 1.0 MU)with elongated, sometimes infolded, poles indicating an overlying membrane. These structures corresponded to the exosporium as seen by transmission EM. The size of the spores, including the cortex (350-550 A), inner membranes, and cytoplasm averaged 5100 X 5900 A. Cytochemical findings suggest that acid mucopolysaccharides and polypeptides containing N-acetyl-neuraminic acid are localized within the exterior and interior layers of the exosporium and at the surface of the outer coat, which could have a tumor inhibiting effect.

Animals↗

Pancreatic neoplasms induced in Syrian golden hamsters. I. Scanning electron microscopic observations.

Pancreases from Syrian golden hamsters treated with N-nitrosobis(2-hydroxy-proply)amine for 10 to 25 weeks were examined under scanning electron microscopy (SEM). Findings indicate that the neoplasms originated from the ductal epithelium and developed progressively. Adenomas were lined by epithelium of differing cells types, ranging from a flat singly ciliated form to cuboidal-columnar types, or to mixed cell populations. The epithelial lining of the ductal carcinomas exhibited tubular and papillary cystic spaces, and cell surfaces were similar to the cuboidal and columnar epithelium of adenomas and of ductal epithelial hyperplasia. However, microvilli were dense and of varied lengths. The SEM observations correlated with patterns seen in routine histologic preparations.

Animals↗

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.

Adenocarcinoma↗

Induction of pancreatic neoplasms by 2,2'-dioxopropyl-N-propylnitrosamine.

A high incidence of pancreatic duct adenomas and carcinomas were induced in Syrian golden hamsters as early as 13 weeks after chronic administration of 2,2'-dioxopropyl-n-propylnitrosamine (DOPN) at a 10 mg/kg dose. In contrast to another pancreatic carcinogen, 2,2'-dihydroxy-propyl-n-propyl-nitrosamine, DOPN induced no tumors of the upper respiratory tract or kidneys, and only a few neoplasms of the lungs and liver.

Adenocarcinoma↗

Carcinogenicity of 4-hydroxybutyl-butylnitrosamine in Syrian hamsters.

4-Hydroxybutyl-butylnitrosamine (HBBN), a urinary metabolite of dibutylnitrosamine (DBN) was shown to induce respiratory and bile duct tumors as well as carcinomas of the urinary bladder in Syrian golden hamsters. This contrasts with results previously obtained in rats and demonstrates that HBBN is not a specific bladder carcinogen. Bronchogenic tumors, seen in DBN-treated hamsters, were not observed after injection of HBBN.

Animals↗