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p53 mutations, O6-alkylguanine DNA alkyltransferase activity, and sensitivity to procarbazine in human brain tumors.
- Source :
-
Cancer [Cancer] 1995 Mar 15; Vol. 75 (6), pp. 1339-42. - Publication Year :
- 1995
-
Abstract
- Background: In human brain tumors, sensitivity to procarbazine as measured by sensitivity in a xenograft tumor model correlated inversely with amounts of the DNA repair enzyme O6-alkylguanine DNA alkyltransferase (AT).<br />Methods: To test the hypothesis that mutations of the p53 tumor suppressor gene in human tumors also can correlate with the response to chemotherapy, p53 mutations2 were identified in primary human malignant brain tumors and cell lines in which AT activity and procarbazine sensitivity in a xenograft model was ascertained.<br />Results: Mutations were identified in 7 of 21 (33%) specimens tested. Specimens containing p53 mutations tended to exhibit an increased growth delay in procarbazine-treated xenografts and lower amounts of AT.<br />Conclusions: p53 mutations in brain tumors may contribute to procarbazine sensitivity by failing to induce arrest at the G1/S cell-cycle checkpoint, thereby preventing the repair of procarbazine-induced genetic alterations.
- Subjects :
- Animals
Base Sequence
Brain Neoplasms drug therapy
Brain Neoplasms pathology
Cell Cycle
DNA Mutational Analysis
DNA Repair
Humans
Mice
Mice, Nude
Molecular Sequence Data
Mutation
Neoplasm Transplantation
O(6)-Methylguanine-DNA Methyltransferase
Polymerase Chain Reaction
Tumor Cells, Cultured
Brain Neoplasms enzymology
Brain Neoplasms genetics
Genes, p53 genetics
Methyltransferases metabolism
Procarbazine therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 0008-543X
- Volume :
- 75
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 7882284
- Full Text :
- https://doi.org/10.1002/1097-0142(19950315)75:6<1339::aid-cncr2820750616>3.0.co;2-f