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Colon preneoplastic lesions in animal models.

Suzui M, Morioka T, Yoshimi N - J Toxicol Pathol (2013)

Bottom Line: These lesions have been induced by commonly used chemical carcinogens such as azoxymethane (AOM), 1,2-dimethylhydrazine (DMH), methylnitrosourea (MUN), or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).Investigators can choose any procedures or methods to examine colonic preneoplastic lesions according to their interests and the objectives of their experiments.Based on topographical, histopathological, and biological features of colon cancer preneoplastic lesions in the animal model, we summarize and discuss the character and implications of these lesions.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Toxicology, Graduate School of Medical Sciences and Medical School, Nagoya City University,1 Kawasumi, Mizuho-ku, Mizuho-cho, Nagoya 467-8601, Japan.

ABSTRACT
The animal model is a powerful and fundamental tool in the field of biochemical research including toxicology, carcinogenesis, cancer therapeutics and prevention. In the carcinogenesis animal model system, numerous examples of preneoplastic lesions have been isolated and investigated from various perspectives. This may indicate that several options of endpoints to evaluate carcinogenesis effect or therapeutic outcome are presently available; however, classification of preneoplastic lesions has become complicated. For instance, these lesions include aberrant crypt foci (ACF), dysplastic ACF, flat ACF, β-catenin accumulated crypts, and mucin-depleted foci. These lesions have been induced by commonly used chemical carcinogens such as azoxymethane (AOM), 1,2-dimethylhydrazine (DMH), methylnitrosourea (MUN), or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Investigators can choose any procedures or methods to examine colonic preneoplastic lesions according to their interests and the objectives of their experiments. Based on topographical, histopathological, and biological features of colon cancer preneoplastic lesions in the animal model, we summarize and discuss the character and implications of these lesions.

No MeSH data available.


Related in: MedlinePlus

Distribution of ACF, MDF, and tumors in each segment (A-J) along the colon. The x-axis indicates the segments from the distal to proximal colon. Each segment was named A to J in 2-cm intervals from the anal side. The y-axis indicates the average number of lesions per colon (multiplicity). At ten (closed diamond) and fourteen weeks (closed triangle) after the start of the experiment, animals were euthanized. After fixing of colon tissues with 10% buffered formalin on a filter paper with the mucosal surface up, colon tissues were stained with a 1% solution of Alcian blue, pH 2.5, in 3% acetic acid for 5 min and immediately washed with distilled water. Subsequently, after detection of MDF, the colon tissue was stained with 0.2% methylene blue solution to identify ACF. ACF, MDF, and tumors were noted grossly for their location, number, and size as described earlier11. The animal experiment was conducted according to the Institutional Animal Care Guidelines.
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fig_002: Distribution of ACF, MDF, and tumors in each segment (A-J) along the colon. The x-axis indicates the segments from the distal to proximal colon. Each segment was named A to J in 2-cm intervals from the anal side. The y-axis indicates the average number of lesions per colon (multiplicity). At ten (closed diamond) and fourteen weeks (closed triangle) after the start of the experiment, animals were euthanized. After fixing of colon tissues with 10% buffered formalin on a filter paper with the mucosal surface up, colon tissues were stained with a 1% solution of Alcian blue, pH 2.5, in 3% acetic acid for 5 min and immediately washed with distilled water. Subsequently, after detection of MDF, the colon tissue was stained with 0.2% methylene blue solution to identify ACF. ACF, MDF, and tumors were noted grossly for their location, number, and size as described earlier11. The animal experiment was conducted according to the Institutional Animal Care Guidelines.

Mentions: Caderni et al.45 identified specific lesions in the colon of rats treated with AOM. When unsectioned colon tissues were stained with high-iron diamine-Alcian blue (HID-AB), foci of crypts with scarce or absent mucins were seen, and such lesions were first defined as mucin-depleted foci (MDF) (Fig. 1C). In that study, male F344 rats received sc injection of AOM (15 mg/kg body weight) twice. The rats developed approximately 4 and 8 MDF/colon at 7 and 15 weeks, respectively, after the start of the experiment, while 271–289 ACF/colon occurred during the same period. Mutations in β-catenin, Apc, and K-ras genes and cytoplasmic β-catenin expression were found in MDF induced by DMH46,47,48. Among these, β-catenin gene mutations included 32G→A (Asp→Asn), 37C→T (Ser→Phe), 33C→T (Ser→Phe), and 41C→T (Thr→Ile). In DMH studies, MDF exhibit dysplastic features, and the induction rate of MDF is dose dependent45,47. Also, MDF increase in size with time. To examine the multiplicity and distribution of ACF, MDF, and tumors, six-week-old F344 rats were treated with DMH (40 mg/kg body weight sc injection twice a week) followed by 1% dextran sodium sulfate in drinking water. At ten and fourteen weeks after the start of the experiment, animals were euthanized. ACF were mainly found in the middle portion of the colon (Fig. 2AFig. 2.


Colon preneoplastic lesions in animal models.

Suzui M, Morioka T, Yoshimi N - J Toxicol Pathol (2013)

Distribution of ACF, MDF, and tumors in each segment (A-J) along the colon. The x-axis indicates the segments from the distal to proximal colon. Each segment was named A to J in 2-cm intervals from the anal side. The y-axis indicates the average number of lesions per colon (multiplicity). At ten (closed diamond) and fourteen weeks (closed triangle) after the start of the experiment, animals were euthanized. After fixing of colon tissues with 10% buffered formalin on a filter paper with the mucosal surface up, colon tissues were stained with a 1% solution of Alcian blue, pH 2.5, in 3% acetic acid for 5 min and immediately washed with distilled water. Subsequently, after detection of MDF, the colon tissue was stained with 0.2% methylene blue solution to identify ACF. ACF, MDF, and tumors were noted grossly for their location, number, and size as described earlier11. The animal experiment was conducted according to the Institutional Animal Care Guidelines.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3921915&req=5

fig_002: Distribution of ACF, MDF, and tumors in each segment (A-J) along the colon. The x-axis indicates the segments from the distal to proximal colon. Each segment was named A to J in 2-cm intervals from the anal side. The y-axis indicates the average number of lesions per colon (multiplicity). At ten (closed diamond) and fourteen weeks (closed triangle) after the start of the experiment, animals were euthanized. After fixing of colon tissues with 10% buffered formalin on a filter paper with the mucosal surface up, colon tissues were stained with a 1% solution of Alcian blue, pH 2.5, in 3% acetic acid for 5 min and immediately washed with distilled water. Subsequently, after detection of MDF, the colon tissue was stained with 0.2% methylene blue solution to identify ACF. ACF, MDF, and tumors were noted grossly for their location, number, and size as described earlier11. The animal experiment was conducted according to the Institutional Animal Care Guidelines.
Mentions: Caderni et al.45 identified specific lesions in the colon of rats treated with AOM. When unsectioned colon tissues were stained with high-iron diamine-Alcian blue (HID-AB), foci of crypts with scarce or absent mucins were seen, and such lesions were first defined as mucin-depleted foci (MDF) (Fig. 1C). In that study, male F344 rats received sc injection of AOM (15 mg/kg body weight) twice. The rats developed approximately 4 and 8 MDF/colon at 7 and 15 weeks, respectively, after the start of the experiment, while 271–289 ACF/colon occurred during the same period. Mutations in β-catenin, Apc, and K-ras genes and cytoplasmic β-catenin expression were found in MDF induced by DMH46,47,48. Among these, β-catenin gene mutations included 32G→A (Asp→Asn), 37C→T (Ser→Phe), 33C→T (Ser→Phe), and 41C→T (Thr→Ile). In DMH studies, MDF exhibit dysplastic features, and the induction rate of MDF is dose dependent45,47. Also, MDF increase in size with time. To examine the multiplicity and distribution of ACF, MDF, and tumors, six-week-old F344 rats were treated with DMH (40 mg/kg body weight sc injection twice a week) followed by 1% dextran sodium sulfate in drinking water. At ten and fourteen weeks after the start of the experiment, animals were euthanized. ACF were mainly found in the middle portion of the colon (Fig. 2AFig. 2.

Bottom Line: These lesions have been induced by commonly used chemical carcinogens such as azoxymethane (AOM), 1,2-dimethylhydrazine (DMH), methylnitrosourea (MUN), or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).Investigators can choose any procedures or methods to examine colonic preneoplastic lesions according to their interests and the objectives of their experiments.Based on topographical, histopathological, and biological features of colon cancer preneoplastic lesions in the animal model, we summarize and discuss the character and implications of these lesions.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Toxicology, Graduate School of Medical Sciences and Medical School, Nagoya City University,1 Kawasumi, Mizuho-ku, Mizuho-cho, Nagoya 467-8601, Japan.

ABSTRACT
The animal model is a powerful and fundamental tool in the field of biochemical research including toxicology, carcinogenesis, cancer therapeutics and prevention. In the carcinogenesis animal model system, numerous examples of preneoplastic lesions have been isolated and investigated from various perspectives. This may indicate that several options of endpoints to evaluate carcinogenesis effect or therapeutic outcome are presently available; however, classification of preneoplastic lesions has become complicated. For instance, these lesions include aberrant crypt foci (ACF), dysplastic ACF, flat ACF, β-catenin accumulated crypts, and mucin-depleted foci. These lesions have been induced by commonly used chemical carcinogens such as azoxymethane (AOM), 1,2-dimethylhydrazine (DMH), methylnitrosourea (MUN), or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Investigators can choose any procedures or methods to examine colonic preneoplastic lesions according to their interests and the objectives of their experiments. Based on topographical, histopathological, and biological features of colon cancer preneoplastic lesions in the animal model, we summarize and discuss the character and implications of these lesions.

No MeSH data available.


Related in: MedlinePlus