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Biomedical subjects

D G Scarpelli

Publications and source records attributed to D G Scarpelli.

At least 73 records · Page 4Linked to original sources
PubMed1982

Response of chemically induced hepatocytelike cells in hamster pancreas to methyl clofenapate, a peroxisome proliferator.

Administration of N-nitrosobis (2-oxopropyl)amine during peak DNA synthesis of regenerating pancreas in hamsters has been shown to induce hepatocytelike cells in pancreas. We now present evidence to demonstrate that such cells respond to methyl clofenapate, a peroxisome proliferator. The response includes a marked proliferation of peroxisomes and enhanced activity of peroxisomal enzymes enoyl-CoA hydratase (8.5- to 13-fold), [1-14C]-palmitoyl-CoA oxidation (2.8- to 3.9-fold), catalase (1.6 to 3.4-fold), and carnitine acetyltransferase (greater than 2,000-fold). Cytochemical localization of catalase by the alkaline 3,3'-diaminobenzidine procedure and immunofluorescence localization of heat-labile enoyl-CoA hydratase showed that these peroxisome-associated enzymes are localized strictly in pancreatic hepatocytelike cells, while adjacent acinar, duct, and islet cells appeared consistently negative. Morphometric analyses of hepatocytelike cells showed a significant increase in the numerical density and an eightfold increase in the volume density of peroxisomes in methyl clofenapate treated animals. These results demonstrate that the hepatocytelike cells are responsible for the observed peroxisomal enzyme activity in pancreas of hamsters and suggest that the derepressed peroxisome specific genes in these cells respond to a peroxisome proliferator as do parenchymal cells in hamster liver.

Butyrates↗
PubMed1982

The absence of gamma-glutamyl transpeptidase activity in putative preneoplastic lesions and in hepatocellular carcinomas induced in rats by the hypolipidemic peroxisome proliferator Wy-14,643.

Administration of Wy-14,643, a hypolipidemic agent which induces peroxisome proliferation, at a concentration of 0.1% (w/w) in the diet, leads to the development of altered foci, neoplastic nodules and hepatocellular carcinomas (HCC) in the liver of rats between 21 and 70 weeks. These various lesions in liver were analyzed histochemically for gamma-glutamyl transpeptidase (GGT) activity. The presence of lipofuscin, a putative indicator of lipid peroxidation was evaluated by autofluorescence. All the altered foci, neoplastic nodules and HCC were consistently negative for GGT, and had small amounts of lipofuscin contrasted to large deposits of this pigment in the surrounding normal liver. These results indicate that GGT is not a phenotypic marker in Wy-14,643 induced hepatic carcinogenesis. Whether the neoplastic alterations induced in liver by other peroxisome proliferators are similarly GGT negative remains to be determined.

Acyltransferases↗
PubMed1982

Human pancreatic adenocarcinoma line Capan-1 in tissue culture and the nude mouse: morphologic, biologic, and biochemical characteristics.

Human pancreatic ductal adenocarcinoma line Capan-1 was studied in tissue culture and the nude mouse. In tissue culture, the neoplastic cells grew as large epithelial-like mucin-producing cells. Subcutaneous and intraperitoneal transplantation of neoplastic cells into nude mice resulted in tumor formation characterized by marked invasiveness and distant metastases. Histologically, the tumor appeared as a well-differentiated mucin-producing adenocarcinoma morphologically resembling the tumor of origin. Chromosomal analysis showed a human karyotype with a chromosome number between 51-61. Lactate dehydrogenase and beta 2-microglobulin used as tumor markers were present in both tissue culture and the serum of tumor-bearing mice. The neoplasm, which was characterized by an increased level of cAMP, had lost completely the ability to respond to secretin stimulation. The tumor grown in the nude mouse was resistant to treatment with 5-fluorouracil, behavior identical to that of the original tumor. Diphtheria toxin resulted in complete tumor destruction. Because Capan-1 tumor grown in the nude mouse shows morphologic, biologic, and biochemical characteristics similar to the tumor of origin, it may be an invaluable tool in furthering understanding of the biology of human pancreatic cancer.

Adenocarcinoma↗
PubMed1982

Two populations of cells with differing proliferative capacities in atypical acinar cell foci induced by 4-hydroxyaminoquinoline-1-oxide in the rat pancreas.

A single intravenous injection of 4-hydroxyaminoquinoline-1-oxide in male Wistar rats at a dose of 6 mg. per kg. of body weight induced atypical acinar cell foci in 100 per cent of the animals. Atypical acinar cell foci could be classified histologically as basophilic and acidophilic foci and acidophilic nodules. Cells in baseophilic foci were large, contained an irregular nucleus and a markedly basophilic cytoplasm with a few to small number of zymogen granules (zymogen-poor cells). By transmission electron microscopy, these cells showed markedly irregular plasma membranes, a well-developed rough endoplasmic reticulum and a few zymogen granules. Cells in acidophilic foci and nodules contained an intensely eosinophilic granular cytoplasm (zymogen-rich cells) and a large oval to round nucleus. By transmission electron microscopy, the cells showed zymogen-rich cytoplasm and irregular lateral plasma membranes. Mitotic activity was completely absent or very rarely observed in normal pancreas or basophilic foci, in contrast to acidophilic foci and nodules in which a mean value of 2.75 +/- 1.27 per 1000 cells was found. Autoradiography confirmed these differences between the proliferative capacity of cells in basophilic foci (1 +/- 1 labeled nuclei per 1000 cells) and acidophilic foci (23.2 +/- 3.15 labeled nuclei per 100 cells). These studies indicate that 4-hydroxyaminoquinoline-1-oxide induces two types of atypical acinar cell foci with different morphologic features and proliferative capacity.

4-Hydroxyaminoquinoline-1-oxide↗
PubMed1981

Early changes in regenerating hamster pancreas following a single dose of N-nitrosobis (2-oxopropyl)amine (NBOP) administered at the peak of DNA synthesis.

A single dose of N-nitrosobis(2-oxopropyl)amine, a carcinogen for hamster pancreas, was administered to hamsters with regenerating pancreas 60 hours after initiation of regeneration when the maximum number of acinar cells are in S phase of the cell cycle. This led to nucleolar segregation and mitotic abnormalities from which the acinar cells quickly recovered. Two months later there was moderate pancreatic atrophy in which there were populations of acinar cells containing a variable complement of zymogen granules. In addition, there were nests of eosinophilic cells of unknown derivation which, though disposed in configurations resembling acinar cells, differed distinctly from them. They were devoid of the rich concentric lamellar arrays of ER and zymogen granules characteristic of acinar cells. In addition, differences existed in the chromatin pattern of their nuclei and the number and morphology of their mitochondria. These results suggest that NBOP induced the emergence of a new cell population with a phenotype distinctly different from any of the component cells of normal hamster pancreas.

Animals↗
PubMed1981

A transplantable human malignant Schwannoma.

A human malignant Schwannoma was serially transplanted through three generations in nude mice. The tumours grew readily and the take-up rate was 100 per cent. No metastasis was observed in nude mice. Morphological features of the original tumour were strictly maintained through all the transplant generations. The tumour cells of the original and of the transplants showed features of primitive Schwann cells of embryonic nerve trunks.

Adult↗
PubMed1981

Differentiation of regenerating pancreatic cells into hepatocyte-like cells.

Differentiation is the process by which multicellular organisms achieve the specialized functions necessary for adaptation and survival. An in vivo model in the Syrian golden hamster is described in which regenerating pancreatic cells are converted into hepatocyte-like cells, as evidenced by the presence of albumin, peroxisomes, and a variety of morphological markers. These cells are stable after the conversion is triggered by a single dose of the carcinogen N-nitrosobis(2-oxopropyl)amine administered during the S phase in regenerating pancreatic cells. This suggests that, given the proper stimulus, regenerating cells in adult pancreas can be redirected into a totally different pathway of differentiation.

Animals↗
PubMed1981

Carcinogenesis in Syrian hamsters by N-nitroso-2,6-dimethylmorpholine, its cis and trans isomers, and the effect of deuterium labeling.

Groups of 20 Syrian male golden hamsters were treated by gavage with solutions of the cis and trans isomers of N-nitroso-2,6-dimethylmorpholine in olive oil. Two doses of each isomer were given for the same time and the ratios of the concentrations corresponded with the ratio in the normally prepared mixture, 2 parts cis to 1 part trans. The cis isomer was more potent in inducing tumors of the liver and pancreas than the trans isomer. The effect of replacement of hydrogen with deuterium at the positions alpha and beta to the nitroso function on carcinogenic potency was examined by administering by gavage the respective isotopically labeled compounds to groups of 20 male hamsters. Each labeled sample constituted a mixture of cis and trans isomers in the ratio of approximately 2 to 1, and the dose was identical with that of the unlabeled sample of the nitrosamine. The beta deuterium labeled compound was less carcinogenic and the alpha deuterium labeled compound was more carcinogenic than the unlabeled material. There was not significant difference between the isomers in activation to a bacterial mutagen by pancreas microsomes or in binding to DNA of the pancreas.

Animals↗
PubMed1981

Relationship between benzo(a)pyrene-induced DNA base modification and frequency of reverse mutations in mutant strains of Salmonella typhimurium.

Salmonella typhimurium cells (TA98 and TA100) were incubated with [3H]benzo(a)pyrene ([3H]BP) and induced rat liver microsomes. The BP-induced cytotoxicity and His+ reverse-mutation frequencies were determined, and bacterial DNA hydrolysates were chromatographed on Sephadex LH-20. Analysis indicated three principal DNA adducts formed from two diastereoisomeric BP diol-epoxides and a 9-hydroxy-benzo(a)pyrene metabolite. An 8.6-fold increase in TA100 cell concentration in the microsome incubation was paralleled by a 7.2-fold decrease in total adducts per cell and a 7.4-fold decrease in mutation frequency. Separate TA98 incubations were titrated with increasing concentrations of [3H](+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene ([3H]anti BP diol-epoxide), [3H](+/-)-7 beta, 8 alpha-dihydroxy-9 beta, 10 beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene [3H]syn BP diol-epoxide), or [3H]9-hydroxybenzo(a)pyrene. Linear, nonsaturated increases in DNA adduct levels were seen up to the highest observed concentrations of 4.00 microM BP diol-epoxide or 6.00 microM 9-hydroxybenzo(a)pyrene in both TA98 and TA100 cells. The increasing adduct levels were accompanied by linearly increasing mutation frequencies. At equivalent concentrations of the two DP diol-epoxides, an average of 8.2-fold more base substitution mutations (TA100) were seen than frameshift mutations (TA98). The results also indicate significant differences in absolute mutagenic efficiency (mutation frequency/unit modified DNA) between these three covalent DNA ligands (TA98, syn BP diolepoxide greater than 9-hydroxy-4,5-epoxy-benzo(a)pyrene greater than anti BP diol-epoxide; TA100, 9-hydroxy-4,5-epoxy-benzo(a)pyrene greater than syn BP diol-epoxide greater than anti BP diol-epoxide).

Animals↗
PubMed1980

N-nitroso-2,6-dimethylmorpholine-induced hemangiosarcomas in the livers of randombred guinea pigs.

The carcinogenic effect of N-nitroso-2,6-dimethylmorpholine (DMNM) was studied in randombred guinea pigs after repeated administration of this compound by gavage. DMNM was administered at two dose levels (14 and 28 mg/kg body wt) weekly for 23 weeks. All animals were observed until their death or termination of the experiment at 54 and 37 weeks for the 14- and 28-mg dose levels, respectively. At 14 mg, 67% of the animals developed hemangiosarcomas of the liver and 60% developed cholangiomas between 36 and 54 weeks. In addition, a poorly differentiated malignant mesenchymal tumor was observed in 1 animal. At 28 mg, liver hemangiosarcomas were observed in 82% of the animals between 26 and 37 weeks. In addition, in 18% of the animals, bronchioalveolar adenoma (1 animal), hepatocellular carcinoma (1 animal), and malignant lymphoma (1 animal) were also induced. Metastases of hemangiosarcomas to lungs, mesenteries, and lymph nodes were observed in 3 animals of each group.

Animals↗
PubMed1979

Transplantable ductal adenocarcinoma of the Syrian hamster pancreas.

A well-differentiated ductal adenocarcinoma of the Syrian golden hamster induced by N-nitrosobis(2-oxopropyl)amine was transplantable to both nude mice and inbred Syrian hamsters. The tumor grew rapidly in the nude mouse (12-fold increase in size at 45 days) in contrast to its growth in hamster (3-fold increase in size at 45 days). A curious finding associated with the slow-growing tumor in the hamster was an intense infiltration of the neoplasm by polymorphonuclear leukocytes unattended by either necrosis or infection. The neoplasm produced mucin and rapidly and specifically bound 125I-labeled secretin, although the degree of nonspecific binding (40.5%) was higher than that of control hamster pancreas (23%). Unstimulated adenyl cyclase activity (pmol cyclic adenosine 3':5'-monophosphate per mg protein) of the neoplasm was significantly higher [3.76 +/- 0.55 (S.E.)] than that of unstimulated normal hamster pancreas (1.03 +/- 0.44). Secretin did not significantly change the level of cyclic adenosine 3':5'-monophosphate (3.3 +/- 0.56) from the unstimulated level in the neoplasm, in contrast to its effect on normal pancreas where the level was increased 3-fold (3.1 +/- 0.75).

Adenocarcinoma↗