丙卡巴嗪
鸟嘌呤
DNA
癌症研究
分子生物学
脑瘤
细胞毒性T细胞
医学
生物
生物化学
病理
化疗
体外
内科学
长春新碱
核苷酸
环磷酰胺
基因
作者
S. Clifford Schold,Thomas P. Brent,Eric von Hofe,H. S. Friedman,Sankar Mitra,Darell D. Bigner,James A. Swenberg,Paul Kleihues
标识
DOI:10.3171/jns.1989.70.4.0573
摘要
✓ The level of O 6 -alkylguanine-deoxyribonucleic acid (DNA) alkyltransferase (AT) was determined in 15 human brain-tumor xenografts in athymic mice. This enzyme is a primary intracellular repair mechanism for lesions produced at the O 6 position of guanine by a wide range of alkylating agents, including nitrosoureas and procarbazine. Its activity ranged from undetectable in five tumor lines to 2338 fmol/mg protein in N-1941, a human glioblastoma xenograft. The sensitivity of 10 of these xenografts to procarbazine was determined and it was found that four of the five tumor lines with AT levels of more than 100 fmol/mg protein had growth delays after procarbazine treatment of less than 20 days, whereas all five lines with undetectable AT levels had growth delays of over 30 days. The primary cytotoxic DNA adduct produced by procarbazine (namely, O 6 -methylguanine) was found to be significantly higher in two sensitive lines with low AT levels than in a highly resistant line with a high AT level. These data suggest that the AT levels of individual brain tumors can be used as predictive indicators of their susceptibility to drugs that exert their antineoplastic effect primarily by O 6 -alkylation of guanine in nuclear DNA.
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