Genetic Alterations in Brain Tumors Following 1,3-Butadiene Exposure in B6C3F1 Mice
| Autor: | Theodora R. Devereux, Robert C. Sills, Natasha P. Clayton, Ronald L. Melnick, Yan Lachat, Monika E. Hegi, Yongbaek Kim, Hue-Hua L. Hong |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Pathology medicine.medical_specialty Tumor suppressor gene 040301 veterinary sciences Mutation Missense Brain tumor Loss of Heterozygosity Mice Inbred Strains Toxicology medicine.disease_cause Polymerase Chain Reaction 030226 pharmacology & pharmacy Pathology and Forensic Medicine 0403 veterinary science Loss of heterozygosity Mice Neuroblastoma 03 medical and health sciences 0302 clinical medicine Glioma Butadienes medicine Animals Missense mutation PTEN Codon Molecular Biology Mutation Dose-Response Relationship Drug biology Brain Neoplasms DNA Neoplasm Exons 04 agricultural and veterinary sciences Cell Biology medicine.disease Immunohistochemistry Carcinogens Cancer research biology.protein Female Tumor Suppressor Protein p53 Carcinogenesis Gene Deletion |
| Zdroj: | Toxicologic Pathology. 33:307-312 |
| ISSN: | 1533-1601 0192-6233 |
| Popis: | The nervous system of the B6C3F1 mouse has rarely been a target for chemical carcinogenesis in the National Toxicology Program (NTP) bioassays. However, 6 malignant gliomas and 2 neuroblastomas were observed in B6C3F1 mice exposed to 625 ppm 1,3-butadiene (NTP technical reports 288 and 434). These mouse brain tumors were evaluated with regard to the profile of genetic alterations that are observed in human brain tumors. Alterations in the p53 tumor suppressor gene were common. Missense mutations were observed in 3/6 malignant gliomas and 2/2 neuroblastomas and were associated with loss of heterozygosity. Most of the mutations occurred in exons 5–8 of the p53 gene and were G → A transitions, and did not involve CpG sites. Loss of heterozygosity at the Ink4a/Arf gene locus was observed in 5/5 malignant gliomas and 1/1 neuroblastoma, while the PTEN (phosphatase and tensin homologue) gene locus was unaffected by deletions. One of 2 neuroblastomas had a mutation in codon 61 of H-ras, while H-ras mutations were not observed in the malignant gliomas examined. Only 1 brain tumor has been reported from control mice of over 500 NTP studies. This malignant glioma showed no evidence of alterations in the p53 gene or K - and H-ras mutations. It is likely that the specific genetic alterations observed were induced or selected for by 1,3-butadiene treatment that contributed to the development of mouse brain tumors. The observed findings are similar in part to the genetic alterations reported in human brain tumors. |
| Databáze: | OpenAIRE |
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