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). 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. 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. 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.
BACKGROUND: In humanbrain 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). METHODS: To test the hypothesis that mutations of the p53tumor suppressor gene in humantumors also can correlate with the response to chemotherapy, p53 mutations2 were identified in primary humanmalignant brain tumors and cell lines in which AT activity and procarbazine sensitivity in a xenograft model was ascertained. 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. 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.
Authors: Eunjoo Kim; Laurie A Davidson; Roger S Zoh; Martha E Hensel; Bhimanagouda S Patil; Guddadarangavvanahally K Jayaprakasha; Evelyn S Callaway; Clinton D Allred; Nancy D Turner; Brad R Weeks; Robert S Chapkin Journal: Carcinogenesis Date: 2015-12-30 Impact factor: 4.944
Authors: D M O'Rourke; G D Kao; N Singh; B W Park; R J Muschel; C J Wu; M I Greene Journal: Proc Natl Acad Sci U S A Date: 1998-09-01 Impact factor: 11.205