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Oncogene activation and surface markers in mouse lymphomas induced by radiation and nitrosomethylurea
Abstract:
Thymic lymphomas have been induced by gamma-radiation and treatment with the chemical nitrosomethylurea in different mice strains. As indicated by the NIH 3T3 focus forming assay, a significant percentage of the tumors contain activated oncogenes of the ras family (K or N). Cloning and sequencing has enabled us to identify single base mutations as the only significant alteration present in the activated oncogenes. These alterations result in the substitution of amino-acid 12 or 61 of the p21 product of the ras genes. With the use of synthetic oligonucleotides it has been found that the tumors do not all contain the same mutation and in one case so far the normal allele is absent.
Insights
Gamma-radiation and nitrosomethylurea induce thymic lymphomas in mice, often activating ras oncogenes. Single base mutations at specific amino acids in ras genes are identified as the cause of activation in these tumors.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Thymic lymphomas are a type of cancer affecting the thymus.
- Oncogenes, such as the ras family, play a critical role in cancer development.
- Chemical and radiation exposures are known carcinogens.
Purpose of the Study:
- To investigate the molecular mechanisms underlying thymic lymphoma induction by gamma-radiation and nitrosomethylurea.
- To identify specific genetic alterations in activated oncogenes within induced thymic lymphomas.
Main Methods:
- Induction of thymic lymphomas in mice using gamma-radiation and nitrosomethylurea.
- NIH 3T3 focus-forming assay to detect activated oncogenes.
- Cloning and sequencing to identify mutations in ras oncogenes (K-ras, N-ras).
- Oligonucleotide analysis to characterize mutations and assess allele status.
Main Results:
- A significant proportion of induced thymic lymphomas showed activated K-ras or N-ras oncogenes.
- The primary alteration identified was single base mutations within the ras oncogenes.
- These mutations specifically altered amino acid 12 or 61 in the p21 ras protein.
- Tumor heterogeneity was observed, with different mutations present across samples.
- In one instance, the normal (non-mutated) allele of the ras gene was found to be absent.
Conclusions:
- Gamma-radiation and nitrosomethylurea can activate ras oncogenes in mouse thymic lymphomas.
- Specific point mutations in ras genes are key events in the oncogenesis of these tumors.
- The findings highlight the role of ras gene mutations in radiation- and chemically-induced thymic lymphomas.