Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three rats of six males, surviving 22 to 27.5 months after one or two intragastric doses of the monoester pyrrolizidine alkaloid, heliotrine (230 mg/kg body weight), and pretreatment with nicotinamide (350 mg/kg body weight) by pretreatment with nicotinamide (350 mg/kg body weight) by i.p. injections, developed pancreatic islet-cell tumors, accompanied in one of the rats by transitory cell papillomas of the urinary bladder and interstitial testicular tumors and in another by a hepatoma. The lesions in the livers showed progression from megalocytosis, to microscopic hepatocellular hyperplasia, to increasingly larger nodules and hepatoma. One rat, given heliotrine, but no nicotinamide, also developed adenoma of the pancreatic islet cells. Adenomas of the pituitary were present among the experimental and also among the control rats killed between 19 and 27.5 months after the beginning of the experiment, and they are not likely to have been caused by the alkaloid. Heliotrine, in which the crucial double bond in the pyrrolizidine moiety is sterically hindered, appears to be less readily sequestered by the liver and also to affect other organs. Alkylation of nicotinamide at the N-1 position prevents its being reused for coenzyme biosynthesis. Hence, pretreatment of rats with large doses of nicotinamide prevents the depletion of nicotinamide adenine dinucleotide coenzymes and liver necrosis in rats given heliotrine (230 mg/kg body weight).
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PMID:Pancreatic islet-cell and other tumors in rats given heliotrine, a monoester pyrrolizidine alkaloid, and nicotinamide. 16 43

The renal oncogenic activity of streptozotocin in male Holtzman rats was significantly decreased by nicotinamide. Adenomas of the kidney were noted in 77% (21/28) of the animals treated with single iv dose of the streptozotocin, 50 mg/kg, while only 18% (5/28) of animals given nicotinamide ip, 350 mg/kg, 10 min before and 180 min after the same dose of streptozotocin had demonstrable renal tumors. Moreover, the renal adenomas induced by streptozotocin alone occurred sooner and were generally larger when compared with those in the animals treated with the nicotinamide-streptozotocin combination. The 50 mg/kg dose of streptozotocin was diabetogenic in all rats, but the diabetic state was not permanent. Spontaneous recovery from the diabetes was first noted after 8 and 10 months of followup, and after 16 months none of the surviving rats were diabetic.
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PMID:Modification of renal tumorigenic effect of streptozotocin by nicotinamide: spontaneous reversibility of streptozotocin diabetes. 17 79

ADP-ribosylation is a posttranslational modification of proteins that has been related to many cellular events, such as DNA replication and repair, cell proliferation and differentiation. The present studies were performed in order to explore the possible relationship between nuclear protein ADP-ribosylation and RNA transcription in the thyroid gland. Inhibition of RNA transcription by alpha-amanitin and actinomycin D caused a decrease in ADP-ribosylation of 27 and 17%, respectively. Nicotinamide caused a dose-related inhibition of ADP-ribosylation, which was highest at 2 mM (around 90%). At this dose nicotinamide inhibited total RNA transcription by 46%, while the activity due to RNA polymerase II decreased by 50% and that related to RNA polymerases I+III dropped by 24%. These results suggest that inhibition of total nuclear protein ADP-ribosylation is accompanied by a parallel decrease in RNA transcription. Since our previous work has shown that TSH stimulates both nuclear ADP-ribosylation and RNA transcription it may be concluded that these activities follow parallel changes within the thyroid. When the same activities were assayed in normal human and in glands bearing follicular adenoma, RNA polymerase II was increased 4 fold in the latter group, without change in nuclear ADP-ribosylation. These results would suggest that a mechanism, distinct from ADP-ribosylation, may also be involved in the regulation of RNA transcription. This latter might be altered under this pathologic condition.
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PMID:Relationship between nuclear ADP-ribosylation and RNA transcription in calf and human thyroid. 244 64

It is shown that at the initiating stage of procarbazine carcinogenesis in F1 female mice the parenteral administration of nicotinamide or pyridoxine results in a significant decrease in the lung adenoma rate from 77% to 18 or 46%, respectively. Pyridoxal, pyridoxal-5'-phosphate and L-penicillamine did not influence the lung adenoma frequency.
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PMID:[Protective action of nicotinamide and pyridoxine on the initiation stage of carcinogenesis induced in mice by procarbazine]. 296 2

Studies were conducted to examine the insulin and proinsulin synthetic response to glucose in the streptozotocin-nicotinamide--induced rat islet adenoma. Tumors responded to an increase from 3.8 mmol/L to 16.6 mmol/L glucose by increasing incorporation of [3H]-L-leucine into both proinsulin and insulin. Though this response was statistically significant, the stimulation was less than that noted in rat islets, and the variability of incorporation was greater. In addition, the conversion of proinsulin to insulin was generally slow, again with substantial intertumor variation. The recovery of insulin, as well as proinsulin, was significantly higher at the end of four hours of incubation in tumors incubated in 16.6 mmol/L glucose, implicating an insulin-degradative pathway modulated by glucose. Therefore, while the tumor will not replace conventional sources of tissue for insulin biosynthetic experiments, systems utilizing the tumor can serve as an addition to the methodology for studying previously unrecognized or poorly understood intracellular processes within the beta cell.
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PMID:The effect of glucose on insulin and proinsulin synthesis in the streptozotocin-nicotinamide--induced rat islet adenoma. 631 16

Preliminary studies were conducted to develop a cell-free system for insulin biosynthesis using the streptozotocin-nicotinamide--induced rat islet adenoma. Radiolabeled proteins, migrating on steric exclusion chromatography and SDS-gel electrophoresis in the region of insulin and proinsulin, were synthesized in a system prepared from the tumor 800 X g supernatant fraction, rat liver cytosol, and appropriate energy substrates. The proteins were not synthesized by a rat liver cell-free system, and synthesis could be substantially inhibited by the addition of cycloheximide. In addition, it could be shown that the islet proteins were not the products of residual intact cells within the system, nor were they an artifact due to nonspecific binding of [3H]-L-leucine to pre-existing insulin and proinsulin. The radiolabeled material eluting with insulin on steric exclusion chromatography was identified as [3H]-insulin by immunoaffinity column chromatography.
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PMID:The synthesis of insulin and proinsulin in a cell-free system derived from the streptozotocin-nicotinamide--induced rat islet adenoma. 631 18

Lauric acid diethanolamine condensate is widely used in cosmetics, shampoos, soaps, and related consumer products, to which there is extensive human exposure. Because of the lack of information about potential risks associated with long-term exposure, lauric acid diethanolamine condensate, coconut oil acid diethanolamine condensate, and oleic acid diethanolamine condensate were selected as representative of the class of diethanolamides for evaluation of prechronic toxicity and carcinogenic potential. Male and female F344/N rats and B6C3F1 mice were exposed to lauric acid diethanolamine condensate dermally for 14 weeks or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, L5178Y mouse lymphoma cells, cultured Chinese hamster ovary cells, and mouse peripheral blood erythrocytes. 14-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were admin istered 0, 25, 50, 100, 200, or 400 mg lauric acid diethanolamine condensate/kg body weight in ethanol by dermal application for 14 weeks. All animals survived until study termination. Final mean body weights and body weight gains of males receiving 200 or 400 mg/kg were significantly less than those of the vehicle control group. Irritation of the skin at the site of application was observed in males receiving 100 mg/kg or greater and in females receiving 200 or 400 mg/kg. Kidney weights of females administered 200 or 400 mg/kg were significantly greater than those of the vehicle control group. There were dose-dependent increases in the incidences of nonneoplastic lesions of the skin at the site of application, including epidermal and sebaceous gland hyperplasia, chronic inflammation, parakeratosis, and ulcer. 14-WEEK STUDY IN MICE: Groups of 10 male and 10 female mice were admin istered 0, 50, 100, 200, 400, or 800 mg lauric acid diethanolamine condensate/kg body weight in ethanol by dermal application for 14 weeks. All animals survived until the end of the study, and final mean body weights and body weight gains of dosed mice were generally similar to those of the vehicle control groups. Irritation of the skin at the site of application was observed in all males and females administered 400 or 800 mg/kg. The kidney weights of males receiving 100, 400, or 800 mg/kg and females receiving 800 mg/kg were significantly greater than those of the vehicle controls. Liver weights of females administered 200 mg/kg or greater were significantly greater than those of vehicle controls. Increased incidences of nonneoplastic lesions of the skin at the site of application, including epidermal and sebaceous gland hyperplasia, chronic inflammation, parakeratosis, and ulcer, were observed in males and females receiving 200 mg/kg or greater. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were admin istered 0, 50, or 100 mg lauric acid diethanolamine condensate/kg body weight in ethanol by dermal application for 104 or 105 weeks. Survival and Body Weights There were no significant differences between vehicle control and dosed males or females in survival or mean body weights. Pathology Findings There were no chemical-related differences in neoplasm incidences. Dose-related increases occurred in the incidences of nonneoplastic lesions of the skin at the site of application, including epidermal and sebaceous gland hyperplasia, hyperkeratosis, chronic inflammation, parakeratosis, and ulcer. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were admin istered 0, 100, or 200 mg lauric acid diethanolamine condensate/kg body weight in ethanol by dermal application for 105 or 106 weeks. Survival and Body Weights There were no significant differences in survival between vehicle control and dosed males or females. Mean body weights of females that received 200 mg/kg were less than those of the vehicle controls beginning at week 33. Pathology Findings The incidences of hepatocellular adenoma or carcinoma (combined) were significantly increased in dosed females compared to the vehicle controls, as was the incidence of hepatocellular adenoma in the 100 mg/kg female group. There were dose-related increases in the incidences of nonneoplastic lesions of the skin at the site of application, including epidermal and sebaceous gland hyperplasia, hyperkeratosis, chronic inflammation, and parakeratosis. Dosed males had greater incidences of thyroid gland follicular cell focal hyperplasia than did the vehicle controls. GENETIC TOXICOLOGY: Lauric acid diethanolamine condensate was not mutagenic in Salmonella typhimurium strain TA97, TA98, TA100, or TA1535, with or without S9 metabolic activation enzymes. No increase in the frequency of mutant colonies of L5178Y mouse lymphoma cells was noted after exposure to lauric acid diethanolamine condensate, with or without S9. In cytogenetic tests with cultured Chinese hamster ovary cells, lauric acid diethanolamine condensate was shown to induce sister chromatid exchanges, but not chromosomal aberrations, with and without S9. In vivo, no increase in the frequency of micro nucleated normochromatic erythrocytes was observed in peripheral blood samples from male and female mice treated dermally with lauric acid diethanolamine condensate for 14 weeks. CONCLUSIONS: Under the conditions of these 2-year dermal studies, there was no evidence of carcinogenic activity of lauric acid diethanolamine condensate in male or female F344/N rats administered 50 or 100 mg/kg or in male B6C3F1 mice administered 100 or 200 mg/kg. There was some evidence of carcinogenic activity in female B6C3F1 mice based on increased incidences of hepatocellular neoplasms. These increases were associated with free diethanolamine, which was present as a contaminant of lauric acid diethanolamine condensate. Dermal administration of lauric acid diethanolamine condensate to rats and mice for 2 years resulted in increased incidences of epidermal and sebaceous gland hyperplasia, hyperkeratosis, chronic inflammation, and parakeratosis at the site of application. Lauric acid diethanolamine condensate administration also resulted in increased incidences of thyroid gland follicular cell hyperplasia in dosed male mice. Synonyms: N,N-bis(2-hydroxyethyl) dodecanamide; N,N-bis(hydroxyethyl) lauramide; N,N-bis(b-hydroxyethyl) lauramide; bis(2-hydroxyethyl) lauramide; coco diethanolamide; coconut oil amide of diethanolamine; diethanollauramide; N,N-diethanollauramide; N,N-diethanollauric acid amide; lauramide DEA; lauric diethanolamide; lauroyl diethanolamide; lauryl diethanolamide; LDA; LDE Trade names: Clindrol 200 L; Ninol AA62; Onyxol 345; Rewomid DLMS; Rewomid DL 203/S; Richamide 6310; Rolamid CD; Standamidd LD; Steinamid DL 203 S; Super amide L-9A; Super amide L-9C; Synotol L-60; Unamide J-56; Varamid ML 1.
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PMID:NTP Toxicology and Carcinogenesis Studies of Lauric Acid Diethanolamine Condensate (CAS NO. 120-40-1) in F344/N Rats and B6C3F1 Mice (Dermal Studies). 1257 83