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Nan Fang Yi Ke Da Xue Xue Bao = Journal... Jun 2014To establish a zebrafish model of liver fibrosis via diethylnitrosamine (DEN)-induced liver injury.
OBJECTIVE
To establish a zebrafish model of liver fibrosis via diethylnitrosamine (DEN)-induced liver injury.
METHODS
A total of 120 wild-type 3-month-old zebrafish were randomly divided into DEN-treated group and control group. The survival rate and behavioral changes of each group were observed. After treatment with DEN for 2, 4, and 6 weeks, liver index was measured, and liver fibrosis was evaluated with HE staining, Gomori staining and Sirius red staining.
RESULTS
No obvious behavioral change was observed in DEN-treated group during the experiment. Compared with that in control group, the liver index of zebrafish in DEN-treated group showed no significantly changes at the time points of observation. Proliferation of reticulate fibers was found in 30% of zebrafish treated with DEN for 4 weeks, and the rate increased to 80% at 6 weeks when reticulate fibers and collagen fibers actively proliferated to result in fiber collapse and formation of fibrotic nodules.
CONCLUSION
A stable zebrafish liver fibrosis model was successfully established by inducing liver damage to facilitate studies of the pathogenesis of liver fibrosis and screening therapeutic drugs.
Topics: Animals; Diethylnitrosamine; Disease Models, Animal; Liver Cirrhosis; Zebrafish
PubMed: 24968829
DOI: No ID Found -
Die Naturwissenschaften Apr 1965
Topics: Carcinogens; Diethylnitrosamine; Liver Neoplasms; Nitrosamines; Pharmacology; Rabbits; Research; Toxicology
PubMed: 14291221
DOI: 10.1007/BF00609289 -
Journal of Cancer Research and Clinical... May 1979The effect of a single subcutaneous injection of different DEN doses was examined in adult Syrian hamsters observed for life. The minimal effective dose (threshold dose)... (Comparative Study)
Comparative Study
The effect of a single subcutaneous injection of different DEN doses was examined in adult Syrian hamsters observed for life. The minimal effective dose (threshold dose) for neoplastic response, reflected by induction of papillary polyps in the larynx and/or trachea, was 1.03 mg DEN/kg body weight. No tumors were found which could be related to treatment in other segments of the respiratory epithelium nor in other tissues.
Topics: Animals; Cricetinae; Diethylnitrosamine; Dose-Response Relationship, Drug; Female; Laryngeal Neoplasms; Male; Mesocricetus; Neoplasms, Experimental; Nitrosamines; Polyps; Tracheal Neoplasms
PubMed: 468894
DOI: 10.1007/BF00405344 -
Experimental Lung Research Nov 1982Diethylnitrosamine 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 revealed a significant increase in the number of argyrophilic cells of neuroepithelial bodies. These affected cells also exhibited enhanced survival in vitro. After 7 days in culture, argyrophilia, dense-core vesicles, and corticotropin-like immunoreactivity were observed in many of the cells derived from the lungs of carcinogen-exposed hamsters by dissociation with pronase. In addition, nuclei of argyrophilic cells in neuroepithelial bodies of the exposed hamsters were labeled at 60 min following administration of [3H]thymidine. This suggests that the carcinogen stimulates the pulmonary neuroendocrine-like cells to divide. Normally, the component cells of neuroepithelial bodies may originate from nonargyrophilic precursor cells in the surrounding epithelium, as in control hamsters the argyrophilic cells of neuroepithelial bodies appeared labeled only at 8 days after the administration of thymidine. The relationship of the diethylnitrosamine-induced reactions to bronchial carcinoid tumors or small-cell carcinomas of the lung remains to be established.
Topics: APUD Cells; Animals; Autoradiography; Cell Division; Cricetinae; Diethylnitrosamine; Epithelial Cells; Injections, Subcutaneous; Lung; Male; Mesocricetus; Nitrosamines; Staining and Labeling
PubMed: 6188606
DOI: 10.3109/01902148209069655 -
Natural Product Research Mar 2023Hepatocellular carcinoma (HCC) is one of the most fatal cancers around the world and remain asymptomatic in early stage. An alcoholic extract prepared from leaves of L....
Hepatocellular carcinoma (HCC) is one of the most fatal cancers around the world and remain asymptomatic in early stage. An alcoholic extract prepared from leaves of L. (Tropaeolaceae) was assessed for its potential activity against diethylnitrosamine-induced liver carcinoma . Oral administration of the extract significantly decreased the inflammatory marker translation NF-kB and supressed HCC progression in combination with 0.5 Gy gamma radiation via EGF-HER-2 pathway. Histopathological and immunohistopathological features also showed the recovery of a hepatic architecture. Immunohistochemical study showed the and LDR enhancement effect on proapoptotic markers (caspase-3 and Bax) and inhibition of anti-apoptotic factor (BCl2). HPLC-DAD-MS analysis of the extract revealed the annotation of twelve compounds. could mediate a defensive influence against diethylnitrosamine-induced hepatocarcinogenesis and serve as a respectable option in amelioration of the hepatocellular carcinoma development in combination with low dose of gamma radiation.
Topics: Tropaeolum; Carcinoma, Hepatocellular; Plant Extracts; Diethylnitrosamine; Gamma Rays; Liver Neoplasms; Signal Transduction; Liver; ErbB Receptors; Apoptosis
PubMed: 35834717
DOI: 10.1080/14786419.2022.2098958 -
Cytogenetic and Genome Research 2004We have developed a simple liver micronucleus assay using young rats (up to 4 weeks old) to assess cytogenetic damage of chemicals in liver cells. Diethylnitrosamine... (Comparative Study)
Comparative Study
We have developed a simple liver micronucleus assay using young rats (up to 4 weeks old) to assess cytogenetic damage of chemicals in liver cells. Diethylnitrosamine (DEN) was used as a model rodent hepatocarcinogen in this study. Compared to the partial hepatectomy method most commonly used for the liver micronucleus assay, the present assay method showed equal or even higher practicability. The young rat liver micronucleus assay was also characterized for rat strain differences, sampling time after treatment, single treatment vs. split treatment, age of animals, administration route, and staining method. Although based on one model chemical, we propose an acceptable protocol for the micronucleus assay using young rat liver as follows: Up to 4-week-old rats should be used; oral or intraperitoneal administration can be used; single or repeated treatment protocols can be applied; sampling time is 3-5 days after the last treatment; hepatocytes are prepared by the collagenase perfusion method; and cells are stained with the AO-DAPI double staining method.
Topics: Acridine Orange; Administration, Oral; Age Factors; Animals; Carcinogens; Cell Separation; DNA Damage; Diethylnitrosamine; Dose-Response Relationship, Drug; Drug Administration Schedule; Fluorescent Dyes; Hepatectomy; Hepatocytes; Indoles; Injections, Intraperitoneal; Liver; Liver Regeneration; Male; Micronucleus Tests; Mitosis; Rats; Rats, Inbred F344; Rats, Sprague-Dawley
PubMed: 15162055
DOI: 10.1159/000077506 -
International Journal of Environmental... Sep 2021Many nitrosamines are potent carcinogens, with more than 30 listed under California's Proposition 65. Recently, nitrosamine contamination of commonly used drugs for...
Many nitrosamines are potent carcinogens, with more than 30 listed under California's Proposition 65. Recently, nitrosamine contamination of commonly used drugs for treatment of hypertension, heartburn, and type 2 diabetes has prompted numerous Food and Drug Administration (FDA) recalls in the US. These contaminants include the carcinogens NDMA (N-nitrosodimethylamine) and NDEA (N-nitrosodiethylamine) and the animal tumorigen NMBA (N-nitroso-N-methyl-4-aminobutyric acid). NMBA and NDEA are metabolically and/or structurally related to NDMA, an N-nitrosomethyl--alkylamine (NMA), and 12 other carcinogenic NMAs. These nitrosamines exhibit common genotoxic and tumorigenic activities, with shared target tumor sites amongst chemicals and within a given laboratory animal species. We use the drug valsartan as a case study to estimate the additional cancer risks associated with NDMA and NDEA contamination, based on nitrosamine levels reported by the US FDA, cancer potencies developed by California's Proposition 65 program and the US Environmental Protection Agency (EPA), and specific exposure scenarios. These estimates suggest that nitrosamine contamination in drugs that are used long-term can increase cancer risks and pose a serious concern to public health.
Topics: Animals; Carcinogens; Diabetes Mellitus, Type 2; Diethylnitrosamine; Dimethylnitrosamine; Neoplasms; Nitrosamines
PubMed: 34574388
DOI: 10.3390/ijerph18189465 -
Journal of Gerontology Mar 1981Female BALB/c mice were given diethylnitrosamine (DEN) in their drinking water beginning at 2.5, 9.5, and 17 months of age (cumulative dose approximately 300 to 400...
Female BALB/c mice were given diethylnitrosamine (DEN) in their drinking water beginning at 2.5, 9.5, and 17 months of age (cumulative dose approximately 300 to 400 mg/kg body weight) or were untreated. Median times of death for the treatment groups were 193, 168, and 125 days, respectively, after cessation of DEN treatment and were significantly different (p less than .01). Induced tumors in the three respective age groups were of squamous forestomach (88, 87, and 84%), vascular tumors of the liver (11, 13, and 16%), and adenomas of the lung (65, 56, and 54%). Controls had no forestomach or liver tumors and relatively low incidences of lung tumors. The fact that aging mice have similar incidences and types of tumors of the same size and in the same tissues, but at an earlier time, shows that (1) DEN is carcinogenic in aging BALB/c mice; (2) age at treatment does not alter the tumor-susceptible tissue nor types of tumors after DEN treatment; (3) tumor incidences are not affected by age at time of treatment; (4) mice die earlier with induced tumors with increasing age at time of treatment; (5) age-matched non-DEN-treated mice die from different diseases (leukemias) than do DEN-treated mice (stomach and liver tumors). These observations may be related, in part, to an identified age-dependent decrease in immunocompetency or to other age-related changes, such as vascular or hormonal, which could explain temporal advancement in the tumorigenic process.
Topics: Aging; Animals; Diethylnitrosamine; Female; Liver Neoplasms; Lung Neoplasms; Mice; Neoplasms, Experimental; Nitrosamines
PubMed: 7204896
DOI: 10.1093/geronj/36.2.158 -
Carcinogenesis Jul 1986Male Wistar rats received a single injection of ethylnitrosourea (ENU; 140 mg/kg), dimethylnitrosamine (DMN; 10 mg/kg) or methyl methanesulphonate (MMS; 80 mg/kg). After...
Persistence of preclastogenic damage in hepatocytes of rats exposed to ethylnitrosourea, diethylnitrosamine, dimethylnitrosamine and methyl methanesulphonate. Correlation with DNA O-alkylation.
Male Wistar rats received a single injection of ethylnitrosourea (ENU; 140 mg/kg), dimethylnitrosamine (DMN; 10 mg/kg) or methyl methanesulphonate (MMS; 80 mg/kg). After 1, 6, 28 and 56 days liver cells were assayed for the presence of preclastogenic lesions. This was done by analysis of micronuclei in hepatocytes isolated at 2, 3 and 4 days after partial hepatectomy. Treatment with MMS did not give rise to a statistically significant increased micronucleus frequency after the two time intervals tested (1 and 6 days). In contrast, frequencies of micronuclei were significantly enhanced at all time intervals after treatment with either ENU or DMN. These results support our previous conclusion that only those alkylating agents which give rise to substantial DNA O-alkylation are able to induce long-lived preclastogenic damage in rat liver cells. Both after ENU and DMN treatment, frequencies of micronuclei were significantly higher at day 6 than at days 1, 28 and 56. It is postulated that part of the primary preclastogenic lesions (supposed to be DNA adducts) are converted into secondary preclastogenic lesions during the first period after exposure to the chemicals. Apparently, both primary and secondary preclastogenic lesions are gradually lost after day 6. This loss is rather low (less than 25%) after ENU, but more impressive after DMN (approximately 60%). The persistent nature of preclastogenic damage induced by diethylnitrosamine was demonstrated in an experiment which showed that a single dose of this agent (50 mg/kg) had the same clastogenic effect as a fractionated dose (five weekly injections of 10 mg/kg). This result also implies that a threshold dose for induction of micronuclei, if present, must be very low, appreciably below 10 mg/kg.
Topics: Alkylation; Animals; DNA; Diethylnitrosamine; Dimethylnitrosamine; Ethylnitrosourea; Hepatectomy; Liver; Male; Methyl Methanesulfonate; Rats; Rats, Inbred Strains; Time Factors
PubMed: 3719902
DOI: 10.1093/carcin/7.7.1053 -
Biochemical Society Transactions 1975
Topics: Age Factors; Animals; Carbon Dioxide; Carbon Radioisotopes; Diethylnitrosamine; Enzyme Inhibitors; Female; Male; Nitrosamines; Phenobarbital; Pyrazoles; Rats; Triazines
PubMed: 1132560
DOI: 10.1042/bst0030285