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Biomedical subjects

D Nagel

Publications and source records attributed to D Nagel.

At least 109 records · Page 6Linked to original sources
PubMed1980

Metabolism and mutagenicity of N-nitroso-2-methoxy-2,6-dimethylmorpholine in hamsters.

N-Nitroso-2-methoxy-2,6-dimethylmorpholine (MeNDMM) was derived from the cyclic form of N-nitroso-(2-hydroxypropyl)(2-oxopropyl)amine (HPOP), a proposed proximate pancreatic carcinogen for the hamster. MeNDMM was metabolized in vivo by noninbred Syrian golden hamsters to HPOP, which was excreted in urine. In vitro metabolism produced HPOP by cytochrome P450-mediated oxidative demethylation. MeNDMM and HPOP were similarly mutagenic in the Ames Salmonella typhimurium assay, in which hamster liver preparations were used for metabolic activation. MeNDMM, due to its metabolism to HPOP, is probably also a pancreatic carcinogen in the hamster.

Animals↗
PubMed1980

Mutagenic activities of oxidized derivatives of N-nitrosodipropylamine in the liver cell-mediated and Salmonella typhimurium assays.

The mutagenic activity of N-nitrosobis(2-oxopropyl)amine (BOP), N-nitroso(2-hydroxypropyl) (2-oxopropyl)amine (HPOP), N-nitrosobis(2-hydroxypropyl)amine (BHP), N-nitrosomethyl-2-oxopropylamine (MOP), and N-nitrosomethyl-2-hydroxypropylamine (MHP) was examined in the Ames liquid incubation assay, using hamster liver homogenate for metabolic activation, and in the hamster liver cell-mediated V79 cell assay. At similar concentrations, the cell-mediated assay showed a greater mutagenic response over background to these nitrosamines than did the bacterial assay. Also, the relative mutagenic potency in the cell-mediated assay (MOP > MHP > BOP > HPOP > BHP) correlated better than that in the Ames assay (HPOP > MHP greater than or equal to BOP = BHP = MOP) with overall carcinogenic potency in the hamster (MOP > BOP > HPOP > BHP). The liver cell-mediated assay may be an important adjunct to the battery of short-term tests for carcinogenicity prescreening.

Animals↗
PubMed1980

Carcinogenicity of N-nitrosomethyl(2-oxopropyl)amine in Syrian hamsters.

7-Methylguanine was found in hydrolysates of liver and pancreas DNA from Syrian golden hamsters given a single dose of N-[1-14C]nitrosobis(2-oxopropyl)amine (BOP). This led us to examine the carcinogenicity of a potential methylating metabolite of BOP, N-nitrosomethyl(2-oxopropyl)amine (MOP). MOP was found to be a potent pancreatic carcinogen by either single or weekly s.c. injections. A single MOP treatment (25 mg/kg body weight) induced ductular adenomas and/or adenocarcinomas in 80% of the hamsters. A higher incidence of these neoplasms was found in 93% and 87% of animals receiving, respectively, 3.5 and 1.75 mg MOP per kg body weight weekly for life. However, the lower dose (0.87 mg/kg body weight) was less effective, resulting in a 33% tumor incidence. Compared with the known potent pancreatic carcinogen BOP, MOP seemed to have a greater affinity for the pancreas since considerably lower doses were required to induce similar incidences of equivalent pancreatic tumors. Like BOP, MOP caused tumors of the liver (7 to 100% incidence), kidneys (7 to 80% incidence), and vascular system (7 to 27% incidence). However, in contrast to BOP, which was noncarcinogenic to the upper respiratory tract, MOP-treated animals developed a high incidence of nasal cavity tumors (40% after a single treatment and 27 to 100% after weekly injections). The mutagenesis studies using hamster liver cell-mediated V79 cells confirmed the stronger effect of MOP compared to BOP. The assumption that MOP might be a proximate carcinogenic metabolite of BOP could not be substantiated by our methods for determining the in vivo and in vitro metabolites of BOP.

Adenocarcinoma↗
PubMed1980

[The human stapedius reflex by ipsilateral electrical stimulation of the auditory meatal skin (author's transl)].

A modified method for eliciting a stapedius reflex by electrical stimulation of the meatal skin is presented. In contrast to the acoustically elicited stapedius reflex, the electrically-induced response is only ipsilateral, and can be ablated by anesthesia of the meatal skin. Contralateral acoustical and ipsilateral electrical stimulations lead to a summation effect of the amplitude off the stapedius reflex. When presented simultaneously, subthreshold electrical and acoustical stimulations may produce a reflectory contraction of the stapedius muscle. Similar responses can be found in diseases of the middle ear and the facial nerve. The method described is not difficult to perform, is painless to the patient, and can be used objectively in neurotologic testing.

Auditory Threshold↗
PubMed1979

Carcinogenic effect of N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine, a postulated proximate pancreatic carcinogen in Syrian hamsters.

N-Nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) proved to be a potent carcinogen in Syrian golden hamsters. The compound is an in vivo metabolite of N-nitrosobis(2-hydroxypropyl)amine, N-nitrosobis(2-oxopropyl)amine (BOP), and N-nitroso-2,6-dimethylmorpholine and a postulated proximate pancreatic carcinogen in hamsters. As with BOP, HPOP induced a higher incidence of pancreatic ductular adenocarcinomas than did N-nitrosobis(2-hydroxypropyl)amine and N-nitroso-2,6-dimethylmorpholine, and these neoplasms showed a great tendency for invasion and metastasis. Also, HPOP induced tumors of the forestomach, liver, gallbladder, kidneys, and vagina (as did BOP). However, HPOP [unlike BOP, but like N-nitrosobis(2-hydroxypropyl)amine and N-nitroso-2,6-dimethylmorpholine] led to tumor development in the nasal cavity, larynx, trachea, intestine, Harderian gland, lips, and flank organ. The possible mechanisms of HPOP carcinogenicity are discussed.

Animals↗
PubMed1979

Metabolism of three radiolabeled pancreatic carcinogenic nitrosamines in hamsters and rats.

The in vivo metabolism and disposition of three radiolabeled N-nitrosamines which are carcinogenic for the pancreas of the hamster but not the rat have been examined. N-[1-14C]Nitrosobis(2-oxopropyl)amine (BOP), N-[1-14C]nitrosobis(2-hydroxypropyl)amine (BHP), and their suggested proximate pancreatic carcinogenic metabolite N-[1-14C]nitroso-(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) were metabolized and exhaled as 14CO2 to various extents somewhat proportional to their carcinogenic potency. More than 50% of the dose of BOP and HPOP was exhaled as 14CO2, whereas 26% of BHP was excreted this way, and 40% of BHP was excreted unchanged in the urine. Administered BOP was excreted to a small extent in the urine of both species as HPOP and BHP. No other nitrosamine metabolites were detected in urine. HPOP and BHP were detected in the pancreatic juice and bile of both species after administration of BOP and BHP. The results suggest that pancreatic ductular carcinogenesis in the hamster as a result of exposure to BOP is not due to secretion of carcinogenic metabolities in the pancreatic juice or reflux of bile containing nitrosamine metabolites into the ducts. Carcinogen metabolic activation appears to be by an oxidative pathway.

Animals↗
PubMed1979

Carcinogenicity of N-nitrosobis(2-hydroxypropyl)amine and N-nitrosobis(2-oxopropyl)amine in MRC rats.

Weekly sc injections of equitoxic doses of N-nitrosobis(2-hydroxypropyl)amine (BHP) and N-nitrosobis(2-oxopropyl)amine (BOP) to Wister-derived MRC rats induced tumors. The incidence, latency, multiplicity, morphologic type, and distribution of these tumors varied according to the compound given. The esophagus was the main target organ for BHP (100%), followed by the respiratory tract (87%), pharynx (80%), colon and liver (each 73%), kidneys (20%), thyroid gland (20%), and urinary bladder and urethra (each 7%). BOP was ineffective in the esophagus and pharynx but induced a higher incidence of tumors in the kidneys (27%), thyroid gland (60%), urinary bladder (33%), and urethra (73%) and fewer neoplasms in the respiratory tract (20%), colon (67%), and liver (53%). In addition, BOP caused a few, apparently primary, prostate squamous cell carcinomas. The results are compared with results of BHP treatment in Sprague-Dawley rats and with results of BHP and BOP treatment in Syrian golden hamsters.

Animals↗
PubMed1978

Tumors induced in mice by N-methyl-N-formylhydrazine of the false morel Gyromitra esculenta.

Continuous administration of 0.0078% N-methyl-N-formylhydrazine (MFH) in drinking water to 6-week-old outbred Swiss mice for life produced tumors of the liver, lung, gallbladder, and bile duct. The incidences of tumors in these four tissues were 33, 50, 9, and 7%, whereas in the untreated controls they were 1, 18, 0, and 0%, respectively. The higher dose (0.0156% MFH) given under identical conditions had no tumorigenic effect, since it proved too toxic for the animals. Histopathologically, the lesions were classified as benign hepatomas, liver cell carcinomas, adenomas and adenocarcinomas of the lungs, adenomas of the gallbladder, cholangiomas, and cholangiocarcinomas. Since the edible false morel Gyromitra esculenta contains a high amount of MFH, the human population should be dissuaded from consumption of this dangerous mushroom.

Animals↗
PubMed1978

Differential metabolism of geometrical isomers of N-nitroso-2,6-dimethylmorpholine in the hamster.

1. The cis and trans isomers of the pancreatic carcinogen N-nitroso-2,6-dimethylmorpholine have been prepared separately, and their metabolism studied in the Syrian hamster. 2. Both isomers were metabolized by beta-oxidation and ring scission to N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine, the suggested proximate pancreatic carcinogen, and to N-nitrosobis(2-hydroxypropyl)amine. 3. The initial rate of beta-oxidation and urinary excretion of the cis isomer was much greater than for the trans isomer, and this is explained in terms of relative ease of enzymic axial attack. The amounts of metabolites in the 24-h urine were, however, similar. 4. The results suggest that the two isomers would have no different carcinogenic potency with respect to the hamster pancreas.

Animals↗
PubMed1978

Tumor induction with the N'-acetyl derivative of 4-hydroxymethyl-phenylhydrazine, a metabolite of agaritine of Agaricus bisporus.

N'-Acetyl-4-(hydroxymethyl)phenylhydrazine was administered as a 0.0625% solution in drinking water continuously for the life span of Swiss mice, from 6 weeks of age. Compared to that in untreated controls, in treated animals the lung tumor incidence rose from 15 to 34% in females and 22 to 48% in males, whereas the incidence of blood vessel tumors increased from 8 to 32% in females and from 5 to 30% in males. Histopathologically, the tumors were classified as adenomas and adenocarcinomas of the lungs and angiomas and angiosarcomas of the blood vessels. The commonly eaten mushroom Agaricus bisporus contains beta-N-[gamma-L(+)-glutamyl]-4-hydroxymethylphenylhydrazine, which under certain conditions yields 4-hydroxymethylphenylhydrazine and L-glutamic acid. Since 4-hydroxymethylphenylhydrazine is relatively unstable, its acetyl derivative was synthesized for this study. The possible environmental significance of the findings is discussed.

Adenocarcinoma↗
PubMed1978

Arthrographic demonstration of pigmented villonodular synovitis of the knee.

Arthrography of the knee is most frequently used for diagnosis of conditions affecting the cartilage and menisci. In a 40-year-old man with pigmented villonodular synovitis, arthrography demonstrated a characteristic pattern of multiple filling defects. Arthrography may prove to be as useful for diagnosis of synovial lesions as for other intraarticular lesions.

Adult↗
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

Studies on the binding of antibody against mouse lactate dehydrogenase (isoenzyme X) by preimplantation mouse embryos.

The binding of antibodies against LDH-X by preimplantation mouse embryos was studied to detect LDH-X from spermatozoa in embryos after fertilization. Incubation of preimplantation mouse embryos with rabbit anti-mouse-LDH-X-IgG and then with peroxidase-labelled goat anti-rabbit IgG revealed a strong peroxidase staining of the zona pellucida of normal fertilized and unfertilized 1-cell ova. However, the reaction was significantly weaker with both fertilized and unfertilized 1-cell ova from females induced to superovulate and normal and superovulated blastocysts. Pure antibody against mouse LDH-X was obtained by affinity chromatography of the rabbit anti-mouse LDH-X-IgG on pure mouse LDH-X covalently bound to sepharose. The pure antibody against mouse LDH-X reacted immunochemically identically to anti-mouse LDH-X-IgG, but it was not bound by any stage of preimplantation mouse embryos. The IgG fractions which had passed through the affinity column during the purification procedure and which did not contain any anti-LDH-X activity were bound by the zonae of preimplantation mouse embryos in the same manner as was unpurified anti-mouse LDH-X-IgG. Histochemical studies indicated LDH activity only in the embryo proper, but not on the zona pellucida. It is concluded that LDH-X is not present in preimplantation mouse embryos.

Animals↗
PubMed1977

Formation of methylhydrazine from acetaldehyde N-methyl-N-formylhydrazone, a component of Gyromitra esculenta.

Gyromitrin, acetaldehyde N-methyl-N-formylhydrazone, is a toxin present in edible wild mushroom Gyromitra esculenta. At 37 degrees under different acidic conditions (pH 1 to 3), mimicking the milieu of human stomach, gyromitrin is converted to methylhydrazine, a known tumor inducer in mice and hamsters, through an intermediate, N-methyl-N-formylhydrazine. In addition, methylhydrazine is formed in the mouse stomach after p.o. administration of gyromitrin. These findings imply that consumption of G. esculenta could present a carcinogenic, as well as an acutely toxic, health hazard.

Animals↗
PubMed1976

Common metabolites of N-nitroso-2,6-dimethylomorpholine and N-nitroso-bis(2-oxopropyl)amine in the Syrian hamster.

N-Nitroso-2,6-demethylmorpholine (NDMM) administered intraperitoneally to Syrian hamsters was metabolized to N-nitroso-bis(2-hydroxypropy)(2-oxopropyl)amine(HPOP) and N-nitroso-bis(2-hydroxpropyl)amine (BHP) which were identified in blood and urine. The potent pancreatic carcinogen N-nitroso-bis(2-oxoproply)amine was previously shown to form the same metabolites. Preliminary results indicate that NDMM also induces pancreatic and other tumors in Syrian hamsters, similar to those found following BHP treatment.

Aged↗
PubMed1976

Trimethylhydrazine hydrochloride as a tumor inducer in Swiss mice.

A 0.05% solution of trimethylhydrazine hydrochloride (TMH) administered for a lifetime in drinking water to outbred Swiss albino mice, beginning at 6 weeks of age, induced tumors of blood vessels, lungs, and kidneys. The tumor incidences in these tissues in untreated controls were 5,22 and 0%, whereas in the treated groups the corresponding tumor incidences increased to 85, 44, and 6%, respectively. Histopathologically, tumors were classified as angiosarcomas of blood vessels and adenomas of the lungs and kidneys. The study thus demonstrated the tumorigenicity of TMH. Contrary to expectation, the chemical structure modification apparently failed to alter qualitatively the tumorigenic response.

Adenoma↗