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Pandurangan AK, Divya T, Kumar K, Dineshbabu V, Velavan B, Sudhandiran G. Colorectal carcinogenesis: Insights into the cell death and signal transduction pathways: A review. World J Gastrointest Oncol 2018; 10:244-259. [PMID: 30254720 PMCID: PMC6147765 DOI: 10.4251/wjgo.v10.i9.244] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2018] [Revised: 06/05/2018] [Accepted: 06/28/2018] [Indexed: 02/05/2023] Open
Abstract
Colorectal carcinogenesis (CRC) imposes a major health burden in developing countries. It is the third major cause of cancer deaths. Despite several treatment strategies, novel drugs are warranted to reduce the severity of this disease. Adenomatous polyps in the colon are the major culprits in CRC and found in 45% of cancers, especially in patients 60 years of age. Inflammatory polyps are currently gaining attention in CRC, and a growing body of evidence denotes the role of inflammation in CRC. Several experimental models are being employed to investigate CRC in animals, which include the APCmin/+ mouse model, Azoxymethane, Dimethyl hydrazine, and a combination of Dextran sodium sulphate and dimethyl hydrazine. During CRC progression, several signal transduction pathways are activated. Among the major signal transduction pathways are p53, Transforming growth factor beta, Wnt/β-catenin, Delta Notch, Hippo signalling, nuclear factor erythroid 2-related factor 2 and Kelch-like ECH-associated protein 1 pathways. These signalling pathways collaborate with cell death mechanisms, which include apoptosis, necroptosis and autophagy, to determine cell fate. Extensive research has been carried out in our laboratory to investigate these signal transduction and cell death mechanistic pathways in CRC. This review summarizes CRC pathogenesis and the related cell death and signal transduction pathways.
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Affiliation(s)
- Ashok kumar Pandurangan
- Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India
- School of Life sciences, B.S. Abdur Rahman Crescent Institute of Science and Technology, Chennai 600048, India
| | - Thomas Divya
- Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India
| | - Kalaivani Kumar
- School of Life sciences, B.S. Abdur Rahman Crescent Institute of Science and Technology, Chennai 600048, India
| | - Vadivel Dineshbabu
- Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India
| | - Bakthavatchalam Velavan
- Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India
| | - Ganapasam Sudhandiran
- Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India
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Abstract
Colorectal cancer is a heterogeneous disease that afflicts a large number of people in the USA. The use of animal models has the potential to increase our understanding of carcinogenesis, tumor biology, and the impact of specific molecular events on colon biology. In addition, animal models with features of specific human colorectal cancers can be used to test strategies for cancer prevention and treatment. In this review, we provide an overview of the mechanisms driving human cancer, we discuss the approaches one can take to model colon cancer in animals, and we describe a number of specific animal models that have been developed for the study of colon cancer. We believe that there are many valuable animal models to study various aspects of human colorectal cancer. However, opportunities for improving upon these models exist.
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Matsushima K, Yamakawa S, Edamoto H, Yamaguchi Y, Nagatani M, Tamura K. Spontaneous Malignant T-cell Lymphoma in a Young Adult Crl:CD (SD) Rat. J Toxicol Pathol 2010; 23:49-52. [PMID: 22272011 PMCID: PMC3234655 DOI: 10.1293/tox.23.49] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2009] [Accepted: 09/29/2009] [Indexed: 11/30/2022] Open
Abstract
We investigated a case of spontaneous malignant T-cell lymphoma observed in a
19-week-old male Crl:CD (SD) rat. The rat showed paralysis beginning 1 week
before euthanasia. Hematological examination revealed marked lymphocytosis
without distinct atypia. Macroscopically, hepatosplenomegaly and partial atrophy
of the thoracic spinal cord were observed. Microscopically, neoplastic cells
infiltrated into the liver, splenic red pulp, bone marrow and epidural space of
the thoracic spinal cord, while no neoplastic cells were observed in the thymus
and lymph nodes. Moreover, the spinal cord showed focal degeneration due to
compression by marked infiltration of neoplastic cells in the subdural space.
The neoplastic cells were generally small-sized round cells that had a round
nucleus with/without a single nucleolus and scanty cytoplasm.
Immunohistochemically, the neoplastic cells were positive for CD3 and CD8 and
negative for CD79α. Judging from these results, the present tumor in this young
adult rat was diagnosed as malignant T-cell lymphoma.
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Affiliation(s)
- Keita Matsushima
- Pathology Division, Bozo Research Center Inc., 1284 Kamado, Gotemba, Shizuoka 412-0039, Japan
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Sano T, Ozaki K, Kodama Y, Matsuura T, Narama I. Malignant Lymphoma with Severe Infiltrative Growth into Skeletal Muscles in WBN/Kob Rats. J Toxicol Pathol 2009; 22:173-8. [PMID: 22271991 PMCID: PMC3251631 DOI: 10.1293/tox.22.173] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2009] [Accepted: 05/18/2009] [Indexed: 12/02/2022] Open
Abstract
Although spontaneously occurring neoplasms have been reported repeatedly in F344, SD and
Wistar rats, which are commonly used strains for routine toxicologic and carcinogenicity
studies, there are only a few reports of malignant lymphoma or lymphatic leukemia except
for large granular lymphocytic leukemia (LGL) in F344 rats. Malignant lymphoma
(lymphosarcoma) is thought to be uncommon in F344 rats. The authors encountered malignant
lymphomas of the non-LGL leukemia type with characteristic pathologic features in WBN/Kob
rats. The mean age at onset of the disease in all 13 affected rats (8 males and 5 females)
was about 60 weeks. Common and characteristic clinical signs were abnormal gait with hind
limb paralysis. Macroscopically, the enlargement of the lymph nodes, spleen and liver was
slight to moderate. Scattered multiple white-to-gray nodules encompassed the aorta and
assumed a bead-like appearance near the thoracic and lumbar vertebrae.
Histopathologically, neoplastic proliferative changes were predominant in the bone marrow
tissue of the entire body, and many tumor cells infiltrated the spleen and several lymph
nodes. The most striking histological features were constant and severe infiltration of
tumor cells in the adipose tissue and skeletal muscle adjacent the thoracic and lumber
vertebrae. Immunohistochemically, all tumor cells were positive for B-cell markers (PAX-5,
CD79a and CD45) and negative for CD3. From the results of immunohistochemistry and
morphological examination, these tumors were diagnosed as malignant B-cell lymphomas.
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Affiliation(s)
- Tomoya Sano
- Department of Pathology, Faculty of Pharmaceutical Sciences,
Setsunan University, 45–1 Nagaotoge-cho, Hirakata City, Osaka 573-0101, Japan
| | - Kiyokazu Ozaki
- Department of Pathology, Faculty of Pharmaceutical Sciences,
Setsunan University, 45–1 Nagaotoge-cho, Hirakata City, Osaka 573-0101, Japan
| | - Yasushi Kodama
- Laboratory of Molecular and Cellular Toxicology, Faculty of
Pharmaceutical Sciences, Hiroshima International University, 5–1–1 Hirokoshingai, Kure
City, Hiroshima 737-0112, Japan
| | - Tetsuro Matsuura
- Department of Pathology, Faculty of Pharmaceutical Sciences,
Setsunan University, 45–1 Nagaotoge-cho, Hirakata City, Osaka 573-0101, Japan
| | - Isao Narama
- Department of Pathology, Faculty of Pharmaceutical Sciences,
Setsunan University, 45–1 Nagaotoge-cho, Hirakata City, Osaka 573-0101, Japan
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Garner MM, Latimer KS, Mickley KA, Ritzman TK, Nordhausen RW. Histologic, immunohistochemical, and electron microscopic features of a unique pulmonary tumor in cockatiels (Nymphicus hollandicus): six cases. Vet Pathol 2009; 46:1100-8. [PMID: 19605913 DOI: 10.1354/vp.08-vp-0136-g-fl] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
A unique form of pulmonary malignancy develops in cockatiels. This report describes the gross, histologic, electron microscopic, and immunohistochemical features of this tumor in 6 cockatiels. DNA in-situ hybridization for polyomavirus in the neoplasm was also performed. The tumor was comprised predominantly of compact sheets of anaplastic round to polygonal cells. All tumors had a high mitotic index, and had occasional large clear to slightly basophilic intranuclear inclusions that caused peripheral dispersal or complete masking of chromatin. Tumors were invasive but convincing metastases were not observed. Transmission electron microscopy identified intracytoplasmic intermediate filaments, desmosomes between cells, and intranuclear cytoplasmic invaginations corresponding to the intranuclear inclusions in light microscopic sections. Neoplastic cells stained positive for vimentin, lysozyme, and in 1 bird, pan cytokeratin. All 6 pulmonary neoplasms were negative for avian polyomavirus using the FN-19/FN-40 cocktail and the long VP-1 probe. We propose that these tumors may be poorly differentiated carcinomas of pulmonary or thymic origin.
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Affiliation(s)
- M M Garner
- Northwest ZooPath, Monroe, WA 98272, USA.
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Kodama M, Murakami K, Sato R, Okimoto T, Nishizono A, Fujioka T. Helicobacter pylori-infected animal models are extremely suitable for the investigation of gastric carcinogenesis. World J Gastroenterol 2005; 11:7063-71. [PMID: 16437649 PMCID: PMC4725077 DOI: 10.3748/wjg.v11.i45.7063] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2005] [Revised: 06/23/2005] [Accepted: 06/24/2005] [Indexed: 02/06/2023] Open
Abstract
Although various animal models have been developed to clarify gastric carcinogenesis, apparent mechanism of gastric cancer was not clarified in recent years. Since the recognition of the pathogenicity of Helicobacter pylori (H pylori), several animal models with H pylori infection have been developed to confirm the association between H pylori and gastric cancer. Nonhuman primate and rodent models were suitable for this study. Japanese monkey model revealed atrophic gastritis and p53 mutation after long-term infection of H pylori. Mongolian gerbil model showed the development of gastric carcinoma with H pylori infection alone, as well as with combination of chemical carcinogens, such as N-methyl-N-nitrosourea and N-methyl-N-nitro-N'-nitrosoguanidine. The histopathological changes of these animal models after H pylori inoculation are closely similar to those in human beings with H pylori infection. Eradication therapy attenuated the development of gastric cancer in H pylori-infected Mongolian gerbil. Although several features of animal models differ from those seen in human beings, these experimental models provide a starting point for further studies to clarify the mechanism of gastric carcinogenesis as a result of H pylori infection and assist the planning of eradication therapy to prevent gastric carcinoma.
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Affiliation(s)
- Masaaki Kodama
- Department of Gastroenterology, Oita University, Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Oita-gun, Oita 879-55, Japan.
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Spinardi-Barbisan ALT, Kaneno R, Barbisan LF, Viana de Camargo JL, Rodrigues MAM. Chemically induced immunotoxicity in a medium-term multiorgan bioassay for carcinogenesis with Wistar rats. Toxicol Appl Pharmacol 2004; 194:132-40. [PMID: 14736494 DOI: 10.1016/j.taap.2003.09.012] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
A variety of chemicals can adversely affect the immune system and influence tumor development. The modifying potential of chemical carcinogens on the lymphoid organs and cytokine production of rats submitted to a medium-term initiation-promotion bioassay for carcinogenesis was investigated. Male Wistar rats were sequentially initiated with N-nitrosodiethylamine (DEN), N-methyl-N-nitrosourea (MNU), N-butyl-N-(4hydroxybutyl)nitrosamine (BBN), dihydroxy-di-n-propylnitrosamine (DHPN), and 1,2-dimethylhydrazine (DMH) during 4 weeks. Two initiated groups received phenobarbital (PB) or 2-acetylaminofluorene (2-AAF) for 25 weeks and two noninitiated groups received only PB or 2-AAF. A nontreated group was used as control. Lymphohematopoietic organs, liver, kidneys, lung, intestines, and Zymbal's gland were removed for histological analysis. Interleukin (IL)-2, IL-12, interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), IL-10, and transforming growth factor beta1 (TGF-beta1) levels were determined by ELISA in spleen cell culture supernatants. At the fourth week, exposure to the initiating carcinogens resulted in cell depletion of the thymus, spleen and bone marrow, and impairment of IL-2, IL-12, and IFN-gamma production. However, at the 30th week, no important alterations were observed both in lymphoid organs and cytokine production in the different groups. The results indicate that the initiating carcinogens used in the present protocol exert toxic effects on the lymphoid organs and affect the production of cytokines at the initiation step of carcinogenesis. This early and reversible depression of the immune surveillance may contribute to the survival of initiated cells facilitating the development of future neoplasia.
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da Silva Franchi CA, Bacchi MM, Padovani CR, de Camargo JLV. Thymic lymphomas in Wistar rats exposed to N-methyl-N-nitrosourea (MNU). Cancer Sci 2003; 94:240-3. [PMID: 12824916 PMCID: PMC11160241 DOI: 10.1111/j.1349-7006.2003.tb01427.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2002] [Revised: 01/09/2003] [Accepted: 01/15/2003] [Indexed: 11/28/2022] Open
Abstract
The Brazilian Agency for the Environment (IBAMA) recently adopted an alternative medium-term multiple-organ assay system with the Wistar rat strain for detection of the carcinogenic potential of pesticides. Originally, this initiation-promotion protocol was established in Japan with the isogenic Fischer 344 male rat. Among the initiating agents used in that assay, N-methyl-N-nitrosourea (MNU) rapidly induces malignant lymphoma and leukemia and early mortality of rats from different strains. This study was developed to evaluate whether the outbred Wistar rats are also similarly susceptible to MNU. Particularly, it aimed to evaluate the dose-response relationship and to register the MNU-induced pre-neoplasia and neoplasia that may develop in the lympho-hematopoietic system (LHS) of the Wistar rat within a medium-term period. Four groups of male Wistar rats were treated during 2 weeks with vehicle or with MNU (80, 160 or 240 mg/kg body weight, i.p.). After sacrifice at the 12th and 20th weeks, the thymus, spleen, bone marrow, cervical and mesenteric lymph nodes and liver were collected for analysis. At the 20th week, LHS malignant tumors and benign vascular tumors occurred only in the high- and intermediate-dose MNU-treated animals. Four animals treated with 240 mg/kg developed diffuse thymic lymphomas; two others, treated respectively with 240 mg/kg and 160 mg/kg, developed spleen hemangiomas. The present observations indicate that the Wistar strain is as susceptible as other strains to the early development of MNU-induced LHS (pre)neoplasia. Therefore, this strain seems suitable to be used as test system in bioassay protocols that adopt MNU as an initiating agent for carcinogenesis.
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Affiliation(s)
- Carla Adriene da Silva Franchi
- Center for Genotoxins and Carcinogens Evaluation (TOXICAN), Institute of BioSciences, UNESP, Botucatu, 18618-000, SP, Brasil
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Ogiu T, Fukami H, Nishimura M. DNA strand breaks and death of thymocytes induced by N-methyl-N-nitrosourea. J Cancer Res Clin Oncol 1992; 118:23-9. [PMID: 1729257 DOI: 10.1007/bf01192307] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
N-Methyl-N-nitrosourea (MNU) is a potent carcinogen in various sites of experimental animals and induces thymic lymphoma in rats, which has long been hard to induce by any carcinogen. To analyze the action of MNU on thymocytes, DNA strand breaking in thymocytes from the MNU-treated rat and that in MNU-treated cultured thymocytes were assayed. Fluorometric analysis of DNA unwinding (FADU assay), first reported by Birnboim and Jevcak to detect X-ray-induced DNA damage, was modified and applied to detect DNA damage in thymocytes treated with MNU in vitro or in vivo. In the present modified method, cell lysate was admixed with 0.15 M sodium hydroxide, and DNA unwinding was processed at pH 12.0 for up to 2 h at 0 degree C in iced water. Double-stranded DNA remaining after alkaline reaction was detected by binding ethidium bromide and measuring its fluorescence. The severity of DNA damage, both in vivo and in vitro, depended on the MNU concentration. In addition, the sequential survival rate and cell-size distribution of thymocytes treated with MNU in vitro were investigated. A close relationship between the severity of DNA damage and cell death was demonstrated in MNU-treated thymocytes, and DNA damage by a non-cell-killing dose of MNU was detected with this FADU assay. MNU-induced cell death is not programmed as in apoptosis, which is caused in thymocytes physiologically, immunologically and by X-ray irradiation or corticoids.
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Affiliation(s)
- T Ogiu
- Division of Physiology and Pathology, National Institute of Radiological Sciences, Chiba, Japan
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Ogiu T, Hard GC, Magee PN, Jensen DE. Comparison of the acute toxicity of N-nitrosocimetidine with three structurally related carcinogens in the rat. Toxicol Pathol 1986; 14:395-403. [PMID: 3809892 DOI: 10.1177/019262338601400402] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
The acute toxicity of N-nitrosocimetidine, the nitrosated derivative of the histamine H2-receptor blocking agent cimetidine, was compared with the toxicities of three structurally related nitroso compounds known to be potent carcinogens, namely N-methyl-N'-nitro-N-nitrosoguanidine, N-methyl-N-nitrosourea, and N-methyl-N-nitrosourethane, and also with the parent drug cimetidine. The acute toxicity of each compound was investigated in 6-week-old female Fischer-344 rats by estimating the median lethal doses via three different routes of administration, and by assessing the sequence of histopathological alterations induced. According to median lethalities, all three known carcinogens were substantially more toxic than nitrosocimetidine whether administered by the intravenous, intraperitoneal, or oral routes. The widest margin of difference was represented by orally administered N-methyl-N-nitrosourea, the median lethal dose being 59 times greater than oral N-nitrosocimetidine. By this method, the acute toxicities of N-nitrosocimetidine and the parent drug cimetidine were virtually identical for each of the three routes of administration. Sequential histological assessment indicated that the three known carcinogens induced specific pathological alterations mainly in organs which were also known to be targets for their carcinogenic activity. In contrast, no tissue lesions of a specific nature were associated with N-nitrosocimetidine or cimetidine in this study. The comparable results with N-nitrosocimetidine and the parent drug provide biological support for previously obtained biochemical data which suggested that N-nitrosocimetidine is rapidly denitrosated to cimetidine in the rat.
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Ogiu T, Sakura Y, Maekawa A. Sequential observations of thymic lymphoma development induced in 10-week-old F344 rats by N-propyl-N-nitrosourea. ACTA PATHOLOGICA JAPONICA 1985; 35:1191-200. [PMID: 4083001 DOI: 10.1111/j.1440-1827.1985.tb01009.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
N-Propyl-N-nitrosourea (PNU) is a strong carcinogen which induces thymic lymphoma and other tumors in F344 rats. In the present experiment, sequential changes of the thymus, spleen, bone marrow, and other organs were examined histologically in F344 rats which were continuously given PNU in the drinking water. Hematopoietic organs, such as the bone marrow, spleen, and thymus rapidly became hypoplastic. Atrophy of the thymus was followed by repopulation and hyperplasia. The latter was characterized by lymphoblast-like cells and was followed by development of early stage lymphoma, which arose from the 10th experimental week onwards. At first, thymic lymphoma was observed to involve thymic lobes unilaterally, later spreading to bilateral lobes, and at the 16th experimental week, metastatic foci were evident in the bone marrow of one rat. In contrast, hypoplasia of the bone marrow continued until the end of the experiment, while hypoplasia of the red splenic pulp continued until the 12th experimental week. These results indicate that PNU-induced lymphomas arise from within the thymus, although it is not possible to rule out a role for the bone marrow as including target cells of PNU. This PNU-thymic lymphoma system in F344 rats should serve as a good model for the study of experimentally induced thymic lymphoma.
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Altmann HJ, Wester PW, Matthiaschk G, Grunow W, van der Heijden CA. Induction of early lesions in the forestomach of rats by 3-tert-butyl-4-hydroxyanisole (BHA). Food Chem Toxicol 1985; 23:723-31. [PMID: 4043878 DOI: 10.1016/0278-6915(85)90265-0] [Citation(s) in RCA: 43] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BHA was administered to Wistar rats at a dose level of 2% in a powdered diet for periods of 1, 2 and 4 wk. After 1 wk epithelial damage, mild hyperplasia and hyperkeratosis of the forestomach mucosa was observed. The hyperplasia and hyperkeratosis showed progression at wk 2 and 4 whereas other epithelial defects regressed. The lesions were most pronounced in the vicinity of the limiting ridge. A further 4 wk of feeding without BHA resulted in a complete regression of epithelial defects, although the hyperplastic changes were still apparent. Other rats were given 1 g BHA/kg body weight/day by gastric intubation in arachis oil for 1, 2, 4, 8, 16 or 32 days. Increased mitotic activity was observed after 1 day and mild hyperplasia after the second intubation, but inflammatory response and superficial defects were not prominent and the hyperplasia of the squamous epithelium did not appear to result from initial damage and subsequent hyper-regenerative activity. A gradual regression of the hyperplastic changes occurred after eight daily intubations. The lesions were found in the apex of the forestomach remote from the limiting ridge. It is concluded that BHA incorporated in powdered diet or given in arachis oil by oral intubation causes lesions in the rat forestomach similar to that reported for BHA given in a pelleted diet (Ito et al. J. natn. Cancer Inst. 1983, 70, 343; idem, Gann 1983, 74, 459). The hyperplastic changes in the mucosa occur rapidly and their localization is dependent on the mode of application. Following withdrawal of the BHA there was almost complete regression of the lesion, only a residual mild hyperplasia remaining after 4 wk.
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Reibel J. Carcinogenesis in forestomach and changes in oral mucosa of rats induced by intragastric N-methylnitrosourea. SCANDINAVIAN JOURNAL OF DENTAL RESEARCH 1982; 90:382-9. [PMID: 6960468 DOI: 10.1111/j.1600-0722.1982.tb00751.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
It is well known that oral administration of N-methylnitrosourea (NMU) induces carcinomas in the forestomach of experimental animals. As the rat forestomach is lined with an orthokeratinized squamous epithelium the purpose of the present study was to elucidate whether carcinogenesis in this localization following intragastric application of NMU was comparable to oral carcinogenesis in experimental animals and humans. Furthermore, the development of oral mucosal lesions in the rats was studied. It is concluded that the morphologic changes seen during carcinogenesis in the forestomach do not seem to differ essentially from those seen during experimental and human oral carcinogenesis. Furthermore, the number of oral lesions found in the present study are higher than reported in other strains of rats following administration of NMU.
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Holmstrup P, Dabelsteen E, Reibel J, Harder F. Normal keratinized mucosa transplants in nude mice. Acta Odontol Scand 1981; 39:187-93. [PMID: 6172954 DOI: 10.3109/00016358109162279] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Two types of normal keratinized mucosa were transplanted to subcutaneous sites of nude mice of two different strains. 24 intact specimens of clinically normal human palatal mucosa were transplanted to nude mice of the strain nu/nu NC. The transplants were recovered after 42 d with a recovery rate of 96%. Moreover, 22 intact specimens of normal rat forestomach mucosa were transplanted to nude mice of the strain nu/nu BALB/c/BOM. These transplants were recovered after 21 d with a recovery rate of 63%. The histologic features of the transplants were essentially the same as those of the original tissues. However, epithelial outgrowths from the transplants differed with respect to the pattern of keratinization. The outgrowths of human palatal mucosa transplants were essentially unkeratinized, while the outgrowths of the rat forestomach transplants showed continued keratinization.
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Chang MJ, Koestner A, Palayoor T, Schumm DE, Webb TE. Characteristics of RNA release from rat brain nuclei and effect of neurocarcinogenesis. Biochem Biophys Res Commun 1980; 92:1348-54. [PMID: 6154462 DOI: 10.1016/0006-291x(80)90434-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
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