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Oncogene alterations in rat colon tumors induced by N-methyl-N-nitrosourea
R J Alexander1, J N Buxbaum, R F Raicht
1Research Service, D.V.A. Medical Center, New York, NY 10010.
Abstract:
The authors assayed oncogene alterations in rat colon tumors induced by the direct-acting chemical carcinogen, N-methyl-N-nitrosourea (MNU). DNA isolated from 34 adenomas and eight carcinomas, as well as adjacent normal colon, of 11 rats was assayed by Southern blotting for restriction fragment length polymorphisms and gene amplifications and deletions in 13 oncogenes known to be involved in human or other animal tumors. In addition to finding apparent point mutations or other small alterations in the fos and abl genes in individual rat colon tumors, the authors observed what appear to be larger alterations (ie, rearrangements, or intragenic insertions or deletions) in the H-ras and myb loci in several tumors. In contrast, no changes in the K-ras, N-ras, myc, N-myc, neu, raf, fms, met, and hst genes were seen in any of these tumors. The frequency of myb gene alterations was higher in carcinomas than in adenomas, suggesting that these changes occurred relatively late during tumorigenesis and were not direct effects of the carcinogen. In addition, the finding of alterations in two or three oncogenes in several MNU-induced rat colon tumors suggests the possibility of more widespread genomic lesions in this model.
Insights
Researchers studied oncogene alterations in rat colon tumors caused by N-methyl-N-nitrosourea (MNU). They found changes in H-ras and myb genes, with myb alterations increasing in carcinomas, suggesting late-stage tumor development.
Area of Science:
- Oncology
- Molecular Biology
- Carcinogenesis
Background:
- Chemical carcinogens like N-methyl-N-nitrosourea (MNU) are used to induce tumors in animal models for cancer research.
- Oncogenes play critical roles in cell growth and cancer development, and their alterations are frequently observed in tumors.
Purpose of the Study:
- To investigate oncogene alterations in rat colon tumors induced by MNU.
- To identify specific oncogenes affected by MNU and determine if these alterations correlate with tumor progression.
Main Methods:
- Southern blotting was used to analyze DNA from rat colon tumors (adenomas and carcinomas) and normal tissue.
- Thirteen known oncogenes were examined for restriction fragment length polymorphisms, amplifications, and deletions.
Main Results:
- Alterations were observed in the fos and abl genes, including point mutations.
- Larger alterations, such as rearrangements and intragenic deletions, were found in the H-ras and myb oncogenes in several tumors.
- No changes were detected in K-ras, N-ras, myc, N-myc, neu, raf, fms, met, and hst genes.
- The frequency of myb gene alterations was higher in carcinomas than in adenomas.
Conclusions:
- Oncogene alterations, particularly in H-ras and myb, occur in MNU-induced rat colon tumors.
- Increased myb alterations in carcinomas suggest a role in later stages of tumorigenesis.
- The presence of alterations in multiple oncogenes indicates potential widespread genomic instability in this model.
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