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Proceedings of the National Academy of... Aug 1981Diethylnitrosamine is known to cause squamous cell carcinoma and adenocarcinoma of the lung in Syrian golden hamsters. Sections of lungs obtained from hamsters treated...
Diethylnitrosamine is known to cause squamous cell carcinoma and adenocarcinoma of the lung in Syrian golden hamsters. Sections of lungs obtained from hamsters treated with the systemic carcinogen diethylnitrosamine showed a significant increase in the number of argyrophilic cells of neuroepithelial bodies. The hyperplastic response was retained at least 4 weeks after cessation of treatment. To examine whether these affected cells exhibited enhanced survival in vitro, lung cells were dissociated with Pronase and grown in culture. After 7 days, argyrophilia, dense-cored vesicles, and corticotropin-like immunoreactivity were observed in many of the cells derived from hamsters treated for 5 or 8 weeks. These findings suggest that the endocrine-like cells of neuroepithelial bodies are affected by diethylnitrosamine as evidenced by a numerical increase in vivo and by the properties exhibited by cells in vitro. The relationship of this diethylnitrosamine-induced reaction to bronchial carcinoid tumors or small-cell carcinoma of the lung remains to be established.
Topics: Animals; Cell Division; Cells, Cultured; Cricetinae; Diethylnitrosamine; Disease Models, Animal; Endocrine Glands; Epithelial Cells; Lung; Male; Mesocricetus; Microscopy, Electron; Neurosecretory Systems; Nitrosamines
PubMed: 6946463
DOI: 10.1073/pnas.78.8.5170 -
IARC Scientific Publications 1987beta-Hydroxynitrosamines appear to be refractory to alpha-oxidation, the common pathway of metabolism of simple dialkylnitrosamines. Some years ago, we postulated that... (Review)
Review
beta-Hydroxynitrosamines appear to be refractory to alpha-oxidation, the common pathway of metabolism of simple dialkylnitrosamines. Some years ago, we postulated that nitrosamines bearing a hydroxyl in the beta position may be activated to alkylating agents by metabolic transformation to sulfate conjugates. Recent evidence has provided support for this hypothesis. A sulfate ester of N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (NHPOPA) has been found in the urine of hamsters treated with the nitrosamine. It has also been found that inhibition of sulfotransferases inhibited the development of DNA single-strand breaks in livers of rats treated with several beta-hydroxy-nitrosamines. Alkylation of rat liver DNA in vivo by N-nitroso(2-hydroxyethyl)methylamine (NHEMA) favoured methylation over 2-hydroxyethylation by a factor of 10. The methylation reaction was inhibited by sulfotransferase inhibitors. Thus, sulfation appears to be an important pathway for activation of beta-hydroxy-nitrosamines. There are, however, other pathways, such as the oxidation of the beta-hydroxyl group to a carbonyl, which may also result in the formation of electrophilic species capable of modifying cellular macromolecules.
Topics: Alkylation; Animals; Diethylnitrosamine; Female; Hydroxylation; Male; Methylation; Nitrosamines; Oxidation-Reduction; Rats; Rats, Inbred F344; Structure-Activity Relationship; Sulfates
PubMed: 3316003
DOI: No ID Found -
Mutation Research Jul 1995Different doses of the hepatocarcinogen diethylnitrosamine (DEN) were injected into fertilized turkey eggs 8 days before hatching. The embryos were removed from the eggs...
Different doses of the hepatocarcinogen diethylnitrosamine (DEN) were injected into fertilized turkey eggs 8 days before hatching. The embryos were removed from the eggs after 4 days and liver samples were shock frozen. Mitochondrial DNA (mtDNA) was purified from the samples. Electrophoresis on agarose gels with native mitochondrial DNA and with ribonuclease-treated mitochondrial DNA revealed a DEN-induced effect on the molecular size of the mtDNA. The content of mtDNA of the regular size of 16 kb dose-dependently decreased, whereas the amount of mtDNA fragments of various size increased. Fluorescent staining of the electrophoresis gels allowed the densitometric quantification of the mitochondrial DNA of the regular band at 16 kb and the amount of fragments of irregular size (smear). The diethylnitrosamine-induced effect was dose-dependent over the whole dose range from 1.24 to 6.2 mmol/kg. Even the lowest dose (10 mg DEN per egg) showed clear-cut effects. Mitochondrial damage and malfunction may be mechanistically involved in the neoplastic transformation and in aging phenomena. The in ovo model is a simple and rapid approach for investigations on chemically induced alterations of mtDNA.
Topics: Animals; DNA Damage; DNA, Mitochondrial; Diethylnitrosamine; Liver; Molecular Weight; Mutagenicity Tests; Turkeys
PubMed: 7603493
DOI: 10.1016/0027-5107(95)00021-a -
Indian Journal of Experimental Biology Apr 2007Considering the hepatoprotective properties of Azadirachta indica, the present study was designed to evaluate its preventive effects against diethylnitrosamine (NDEA)...
Considering the hepatoprotective properties of Azadirachta indica, the present study was designed to evaluate its preventive effects against diethylnitrosamine (NDEA) induced hepatotoxicity in male Balb/c mice. Exposure of NDEA caused a significant increase in micronucleated cell score, lipid peroxidation levels (LPO) and activity of lactate dehydrogenase (LDH). A significant decrease in reduced glutathione (GSH) contents and activity of glutathione-S-transferase (GST) was also observed upon NDEA treatment, whereas their activities of cytochrome P450 and cytochrome b5 showed non-significant alterations. Aqueous A. indica leaf extract (AAILE) pretreatment showed protective effects against NDEA induced toxicity by decreasing the frequency of micronucleated cell, levels of LPO and LDH activity. Also, a decreased activity of GST, cytochrome P450 and an increased activity of cytochrome b5, GSH contents was observed when AAILE pretreated mice were injected with NDEA. Only AAILE treatment caused a noticeable decrease in the frequency of micronuclei, activity of cytochrome P450 and cytochrome b5, but a significant increase in the activity of GST and GSH contents, whereas, non significant alterations were observed in the activity of LDH and levels of LPO. Significance of these observations with respect to hepatoprotective efficacy of A. indica has been discussed in the present manuscript.
Topics: Alkylating Agents; Animals; Azadirachta; Chemical and Drug Induced Liver Injury; Cytochrome P-450 Enzyme System; Cytochromes b5; Diethylnitrosamine; Glutathione; Glutathione Transferase; L-Lactate Dehydrogenase; Lipid Peroxidation; Liver; Liver Diseases; Male; Mice; Micronucleus Tests; Plant Extracts; Plant Leaves
PubMed: 17477308
DOI: No ID Found -
Tissue Engineering and Regenerative... Dec 2022Liver inflammation is the main cause of severe liver diseases, including liver fibrosis, steatohepatitis, cirrhosis and hepatocellular carcinoma. Cell therapy topics are...
BACKGROUND
Liver inflammation is the main cause of severe liver diseases, including liver fibrosis, steatohepatitis, cirrhosis and hepatocellular carcinoma. Cell therapy topics are receiving increasingly more attention. The therapeutic applications of mesenchymal stem cells (MSC) have become one of the most discussed issues. While other stem cells have therapeutic effects, they have only one or two clinical applications. MSCs are responsible for repairing a variety of tissue injuries. Moreover, MSCs could be derived from several sources, including adipose tissue. MSCs are usually more abundant and easier to obtain compared to other stem cells.
METHODS
To prove the concept that MSCs have homing ability to the injured tissue and assist in tissue repair, we examined the effects of intravenous injected adipose-derived mesenchymal stem cells (ADSCs) in a N-nitrosodiethylamine (DEN)-induced liver injury rat model.
RESULTS
The significant repairing ability of ADSCs was observed. The levels of fibrosis, apoptosis, and tumorigenesis in the DEN-injured liver tissues all decreased after ADSC treatment. Furthermore, to enhance the therapeutic effects of ADSCs, we pretreated them with L-theanine, which promotes the hepatocyte growth factor secretion of ADSC, and therefore improved the healing effects on injured liver tissue.
CONCLUSION
ADSCs, especially L-theanine-pretreated ADSCs, have anti-inflammation, anti-apoptosis, and anti-tumorigenesis effects on the N-nitrosodiethylamine-induced liver injury rat model.
Topics: Rats; Animals; Mesenchymal Stem Cell Transplantation; Diethylnitrosamine; Chemical and Drug Induced Liver Injury, Chronic; Mesenchymal Stem Cells
PubMed: 36029414
DOI: 10.1007/s13770-022-00472-2 -
Bulletin of Experimental Biology and... Jun 2004Suckling mice were more sensitive to the hepatocarcinogenic effect of various carcinogens compared to adult animals. After treatment with o-aminoazotoluene and...
Suckling mice were more sensitive to the hepatocarcinogenic effect of various carcinogens compared to adult animals. After treatment with o-aminoazotoluene and diethylnitrosamine HNF3-DNA-binding capacity and glucocorticoid-induced liver tyrosine aminotransferase activity in suckling mice decreased more significantly than in adult animals.
Topics: Age Factors; Alkylating Agents; Animals; Animals, Suckling; Carcinogens; Diethylnitrosamine; Female; Glucocorticoids; Liver; Male; Mice; Mice, Inbred CBA; Tyrosine Transaminase; o-Aminoazotoluene
PubMed: 15455081
DOI: 10.1023/b:bebm.0000042708.97983.23 -
European Journal of Cancer & Clinical... Sep 1986The present work has been planned in order to elucidate the effect of phenobarbital (PB: 15 mg per rat of ingested dose) on carcinogenesis when it is administered...
The present work has been planned in order to elucidate the effect of phenobarbital (PB: 15 mg per rat of ingested dose) on carcinogenesis when it is administered simultaneously with diethylnitrosamine (DEN: 10 mg/kg/day). Wistar rats (180 g) were treated by DEN alone or by DEN + PB during 2, 4 and 6 weeks according to our schedule for hepatocarcinogenesis. After the end of the treatment, the number and the size of induced PAS positive preneoplastic foci was significantly reduced when PB was given simultaneously with DEN for 4 and 6 weeks. The mitotic inhibition and the production of micronuclei normally observed after partial hepatectomy in DEN treated rats were also significantly decreased in DEN + PB treated rats. When the treatment last only 2 weeks, the presence of PB did not change significantly the last parameters. In DEN + PB treated rats, the survival was prolonged and the tumor incidence decreased as compared with the results obtained by DEN alone. It is concluded that PB, which promotes carcinogenesis when administered after the DEN treatment, reduces the carcinogen effect when given simultaneously with DEN. This 'anti-carcinogen' effect acts on the initiation as well as on the promotion of the precancerous lesions. Biochemical investigations are in progress to obtain more information about this 'paradoxical' PB effect.
Topics: Animals; Diethylnitrosamine; Drug Interactions; Liver Neoplasms, Experimental; Male; Mitotic Index; Phenobarbital; Precancerous Conditions; Rats; Rats, Inbred Strains
PubMed: 3780814
DOI: 10.1016/0277-5379(86)90008-8 -
Experientia May 1977
Topics: Chemical Phenomena; Chemistry; Diethylamines; Diethylnitrosamine; Methods; Nitrogen Dioxide; Nitrosamines
PubMed: 862774
DOI: 10.1007/BF01946507 -
Proceedings of the Society For... Nov 1985Using a newborn rat model for carcinogenesis, changes in liver cytosolic proteins at three stages of tumorigenesis, on Days 21, 97, and 120, by mirex... (Comparative Study)
Comparative Study
Using a newborn rat model for carcinogenesis, changes in liver cytosolic proteins at three stages of tumorigenesis, on Days 21, 97, and 120, by mirex (dodecachloropentacyclo-1,3,4-metheno-2H-cyclobuta[cd] pentalene), and diethyl- and dimethylnitrosamines (DEN and DMN) were studied. Following multiple exposure to the hepatocarcinogens, groups of weanling rats were given dietary phenobarbital (PB) up to 120 days. SDS-PAGE separation of cytosolic proteins showed that at 21 days, prior to PB, two proteins of 26K and 23K mol wt were significantly induced by mirex and DMN while a high mol wt 63K protein was induced only by DEN and DMN. During the period of PB treatment up to 97 days, these proteins were well sustained at a higher level. A marked increase in 21K protein band was also observed at this point. In tumor tissues obtained from DEN and DMN rats continued on PB diet for 120 days, the high level of 63K protein was seen only in DEN and not in DMN tumor. The tumors also showed a significant reduction in 25K protein compared to 21- and 97-day groups. The presence of even lower mol wt proteins of 14-21K was seen in tumors. The early detection and further characterization of these low mol wt proteins may provide clues as to whether they are preneoplastic markers or oncogene products as speculated by other investigators. Moreover, certain similarities in the induction of cytosolic proteins by "epigenetic" and "genotoxic" carcinogens raise more interesting questions regarding the mechanisms of action of these distinct classes of carcinogens.
Topics: Animals; Carcinogens; Cocarcinogenesis; Cytosol; Diethylnitrosamine; Dimethylnitrosamine; Female; Insecticides; Liver; Liver Neoplasms; Male; Mirex; Neoplasm Proteins; Phenobarbital; Precancerous Conditions; Protein Biosynthesis; Rats; Rats, Inbred Strains
PubMed: 4048162
DOI: 10.3181/00379727-180-42166 -
Biochemical and Biophysical Research... Aug 1987We have investigated the generation of prooxidant state shortly after administration of N-nitrosamines (NA) to rats. N-Nitrosodimethylamine (NDMA) was found to increase...
We have investigated the generation of prooxidant state shortly after administration of N-nitrosamines (NA) to rats. N-Nitrosodimethylamine (NDMA) was found to increase ethane exhalation (EE) rapidly in a dose-related manner. EE remained elevated for several days after single doses of NDMA. Similarly, lipid peroxidation (LP) in the liver (measured by four methods) increased rapidly showing a peak 20 min after NDMA dose. The increase of LP was preceded by a decrease in retinol concentration in the liver. N-Nitrosodiethanolamine, too, increased EE and LP in the liver, whereas N-nitrosomethylbenzylamine had no effect. Thus, hepatocarcinogenic NA induced LP in their target tissue, and the LP enhancing effects of NA were not related to their acute toxic effects.
Topics: Animals; Carcinogens; Diethylnitrosamine; Dimethylnitrosamine; Ethane; Glutathione; Kinetics; Lipid Peroxides; Liver; Male; Nitrosamines; Peroxidases; Rats; Rats, Inbred Strains; Structure-Activity Relationship; Vitamin A
PubMed: 3619914
DOI: 10.1016/0006-291x(87)90753-4