Experimental Intestinal Cancer Research with Special Reference to Human Pathology

Pozharisski, Kazymir M.; Likhachev, A.; Klimashevski, V.F.; Shaposhnikov, Jacob D.

doi:10.1016/s0065-230x(08)60897-0

Cited by 66 publications

(22 citation statements)

References 201 publications

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“…PhIP is one of the most abundant heterocyclic amines present in our environment (Felton and Knize, 1991;Layton et al, 1995;Wakabayashi et al, 1992). Initiation/promotion bioassays using DMH or azoxymethane (AOM) as initiators have been developed to detect modifying activity of test chemicals on rodent colon carcinogenesis (Pozharisski et al, 1979;Rogers and Nauss, 1985;Shirai et al, 1985). Recently, it was thereby shown that an antioxidant, 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), can inhibit colon tumor development driven by PhIP as a second-stage carcinogen and/ or promoter in male F344 rats .…”

Section: Introductionmentioning

confidence: 99%

Prevention by natural food anthocyanins, purple sweet potato color and red cabbage color, of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-associated colorectal carcinogenesis in rats initiated with 1,2-dimethylhydrazine.

Hagiwara¹,

et al. 2002

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-The potential of purple sweet potato color (PSPC) and red cabbage color (RCC), natural anthocyanin food colors, to modify colorectal carcinogenesis was investigated in male F344/DuCrj rats, initially treated with 1,2-dimethylhydrazine (DMH) and receiving 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) in the diet. After DMH initiation, PSPC and RCC were given at a dietary level of 5.0% in combination with 0.02% PhIP until week 36. No PSPC or RCC-treatment-related changes in clinical signs and body weight were found. Incidences and multiplicities of colorectal adenomas and carcinomas in rats initiated with DMH were clearly increased by PhIP. In contrast, lesion development was suppressed by RCC, or tended to be inhibited by PSPC administration. Furthermore, in the non-DMH initiation groups, induction of aberrant crypt foci (ACF) by PhIP was significantly decreased by RCC supplementation. The results thus demonstrate that while PhIP clearly exerts promoting effects on DMH-induced colorectal carcinogenesis, these can be reduced by 5.0% PSPC or 5.0% RCC in a diet under the present experimental conditions.

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Section: Introductionmentioning

confidence: 99%

Prevention by natural food anthocyanins, purple sweet potato color and red cabbage color, of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-associated colorectal carcinogenesis in rats initiated with 1,2-dimethylhydrazine.

Hagiwara¹,

et al. 2002

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“…(9) DMH-induced colon tumors in rodents are very close to human colon cancer with regard to morphology, pattern of growth and clinical manifestations. (10) Colorectal adenocarcinomas, induced by DMH in mice, often invade into the submucosa and muscular layer, but those induced by AOM and methylazoxymethanol did not show such biological and histological natures. (10,11) However, the major weakness of the model, using DMH, is that multiple injections of DMH and long-term experimental period are required to induce colon tumors in laboratory animals.…”

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confidence: 97%

“…(10) Colorectal adenocarcinomas, induced by DMH in mice, often invade into the submucosa and muscular layer, but those induced by AOM and methylazoxymethanol did not show such biological and histological natures. (10,11) However, the major weakness of the model, using DMH, is that multiple injections of DMH and long-term experimental period are required to induce colon tumors in laboratory animals. β-Catenin, acting as a structural protein at cell-cell adherens junctions and as a transcriptional activator mediating Wnt signal transduction, (12) participates in a large cytoplasmic protein complex, which contains the tumor suppressor gene product of adenomatous polyposis coli (APC), glycogen synthase kinase-3β (GSK-3β) and axin/ conductin.…”

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confidence: 97%

β‐Catenin mutations in a mouse model of inflammation‐related colon carcinogenesis induced by 1,2‐dimethylhydrazine and dextran sodium sulfate

et al. 2005

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In a previous study, we developed a novel mouse model for colitisrelated carcinogenesis, utilizing a single dose of azoxymethane (AOM) followed by dextran sodium sulfate (DSS) in drinking water. In the present study, we investigated whether colonic neoplasms can be developed in mice initiated with a single injection of another genotoxic colonic carcinogen 1,2-dimethylhydrazine (DMH), instead of AOM and followed by exposure of DSS in drinking water. Male crj: CD-1 (ICR) mice were given a single intraperitoneal administration (10, 20 or 40 mg/kg body weight) of DMH and 1-week oral exposure (2% in drinking water) of a non-genotoxic carcinogen, DSS. All animals were killed at week 20, histological alterations and immunohistochemical expression of β β β β-catenin, cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS) were examined in induced colonic epithelial lesions (colonic dysplasias and neoplasms). Also, the β β β β-catenin gene mutations in paraffin-embedded colonic adenocarcinomas were analyzed by the single strand conformation polymorphism method, restriction enzyme fragment length polymorphism and direct sequencing. The incidences of colonic neoplasms with dysplastic lesions developed were 100% with 2.29 ± ± ± ± 0.95 multiplicity, and 100% with 10.38 ± ± ± ± 4.00 multiplicity in mice given DMH at doses of 10 mg/kg or 20 mg/kg and 2%DSS, respectively. Although approximately half of the mice given DMH at a dose of 40 mg/kg bodyweight were dead after 2-3 days after the injection, mice who received DMH 40 mg/kg and 2%DSS had 100% incidence of colonic neoplasms with 9.75 ± ± ± ± 6.29 multiplicity. Immunohistochemical investigation revealed that adnocarcinomas, induced by DMH at all doses and 2%DSS, showed positive reactivities against β β β β-catenin, COX-2 and iNOS. In DMH/ DSS-induced adenocarcinomas, 10 of 11 (90.9%) adenocacrcinomas had β β β β-catenin gene mutations. Half of the mutations were detected at codon 37 or 41, encoding serine and threonine that are direct targets for phosphorylation by glycogen synthase kinase-3β β β β. The present results suggests that, as in the previously reported model (AOM/DSS) our experimental protocol, DMH initiation followed by DSS, may provide a novel and useful mouse model for investigating inflammation-related colon carcinogenesis and for identifying xenobiotics with modifying effects. (Cancer Sci 2005; 96: 69-76) C olorectal cancer (CRC) is one of the most common nonsmoking related cancers. The risk for CRC is associated with extent and duration of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease.(1,2) The etiopathogenesis of IBD remains uncertain, although it is generally assumed that chronic inflammation is the primary driving force.(3) To understand the pathogenesis of IBD and IBD-related CRC, several animal models were reported. The chemically induced and genetic models of colonic inflammation do not completely mimic the disease situation found in UC patients, (4) although they are more readily available, reproduci...

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“…as confirmed by our study. The histopathologic fea tures of AOM-induced tumors closely resemble those of human colorectal adenocarcinomas [9][10][11]13]. In addi tion, the distribution of colonic tumors at high doses of carcinogen resembles the distribution in human popula tions with the highest risk of colonic cancer.…”

Section: Discussionmentioning

confidence: 99%

Lack of Evidence for Adenoma-Carcinoma Sequence in Chemically Induced Colonic Carcinogenesis in Rats

et al. 1985

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The rat model of azoxymethane-induced colonic carcinogenesis was evaluated for the occurrence of an adenoma-carcinoma sequence analogous to that in human beings. Male 10-week-old Fischer 344 rats were given 10 weekly subcutaneous injections of azoxymethane at a dose of 15 mg/kg. Every 2 weeks after the first dose, 5 animals were necropsied. A colon tumor was identified first at week 10. At week 16, at least 60% of the rats generally had a colon tumor. The mean size of the tumors tended to increase progressively during the study. Histopathologic examination showed invasion of the muscularis mucosae or deeper layers of the colonic wall in 74% of the tumors. Invasion was unrelated to the size of the tumors, being identified in even the smallest tumors of 1–2 mm of diameter. Invasion was also unrelated to the severity of dysplasia in the tumors, occurring in 83 % of the tumors with low-grade dysplasia, but in 69% of the tumors with high-grade dysplasia. No tumor showed the histopathologic features of an adenoma giving rise to an invasive carcinoma. The findings indicate that an adenoma-carcinoma sequence analogous to that in human beings does not occur in the rat model of azoxymethane-induced colonic carcinogenesis.

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Experimental Intestinal Cancer Research with Special Reference to Human Pathology

Cited by 66 publications

References 201 publications

Prevention by natural food anthocyanins, purple sweet potato color and red cabbage color, of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-associated colorectal carcinogenesis in rats initiated with 1,2-dimethylhydrazine.

Prevention by natural food anthocyanins, purple sweet potato color and red cabbage color, of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-associated colorectal carcinogenesis in rats initiated with 1,2-dimethylhydrazine.

β‐Catenin mutations in a mouse model of inflammation‐related colon carcinogenesis induced by 1,2‐dimethylhydrazine and dextran sodium sulfate

Lack of Evidence for Adenoma-Carcinoma Sequence in Chemically Induced Colonic Carcinogenesis in Rats

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