Spontaneous and Thiazolidinedione-Induced B6C3F1 Mouse Hemangiosarcomas Exhibit Low ras Oncogene Mutation Frequencies
| ISSN: | 0041-008X |
|---|---|
| DOI: | 10.1006/taap.1999.8763 |
| Přístupová URL adresa: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6f9ade2af3b6fd0ef5ffa26d68ec7bbf https://doi.org/10.1006/taap.1999.8763 |
| Rights: | CLOSED |
| Přírůstkové číslo: | edsair.doi.dedup.....6f9ade2af3b6fd0ef5ffa26d68ec7bbf |
| Autor: | Steven K. Duddy, Suzanne M. Gorospe, Michael R. Bleavins, Felix A. de la Iglesia |
| Rok vydání: | 1999 |
| Předmět: |
Male
Hemangiosarcoma Mutagenesis (molecular biology technique) Mice Inbred Strains Biology Toxicology medicine.disease_cause Polymerase Chain Reaction Evolution Molecular Mice Troglitazone Exon medicine Animals Angiosarcoma Chromans Gene Pharmacology Genetics Mutation Oncogene Transition (genetics) DNA Neoplasm Vascular Neoplasms Thiazoles Genes ras Carcinogens Cancer research Female Thiazolidinediones Carcinogenesis Sequence Analysis |
| Zdroj: | Toxicology and Applied Pharmacology. 160:133-140 |
| ISSN: | 0041-008X |
| DOI: | 10.1006/taap.1999.8763 |
| Popis: | Hemangiosarcomasare uncommon malignant endothelial cell tumors in humans and experimental animal species. The mechanisms giving rise to these tumors are poorly understood even though the histotypes are comparable between humans and rodents. Activating mutations in cellular ras protooncogenes have been detected in sporadic and chemically induced human and rodent hemangiosarcomas. Ras activation significantly modulates tumor angiogenesis, suggesting that mutations in ras genes might be causally related to vascular tumorigenesis. To more clearly define the role of ras in experimental vascular tumorigenesis, mutations in the Ki- and Ha-ras genes were characterized in 63 hemangiosarcomas that arose unexpectedly in control and treated B6C3F1 mice during a two-year carcinogenicity study of the thiazolidinedione troglitazone. DNA was extracted from paraffin sections of mouse hemangiosarcomas, control liver, or positive control hepatocellular carcinomas with defined mutations in the Ki- or Ha-ras genes. Exons 1 and 2 of the Ki- and Ha-ras genes were independently amplified using primer extension preamplification/locus-specific heminested PCR, and PCR amplicons were directly sequenced to identify mutations in codons 12, 13, or 61. Activating mutations were detected in 3 of 63 hemangiosarcomas: a single G-->A transition in the second position of Ki-ras codon 13 in a tumor from a treated animal and two G-->T transversions in the second position of Ha-ras codon 13, one in a single tumor from a control animal and one in a tumor from a treated animal. These mutations are consistent with endogenous mutagenesis arising from oxidative DNA damage. The low frequency of mutation ( |
| Databáze: | OpenAIRE |
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