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1
SR 4233 cytotoxicity and metabolism in DNA repair-competent and repair-deficient cell cultures.SR 4233在具备DNA修复能力和缺乏DNA修复能力的细胞培养物中的细胞毒性及代谢情况。
Br J Cancer. 1991 Mar;63(3):358-62. doi: 10.1038/bjc.1991.85.
2
Repair of DNA and chromosome breaks in cells exposed to SR 4233 under hypoxia or to ionizing radiation.在缺氧条件下暴露于SR 4233的细胞或受到电离辐射的细胞中DNA和染色体断裂的修复。
Cancer Res. 1992 Aug 15;52(16):4473-7.
3
Tirapazamine-induced DNA damage measured using the comet assay correlates with cytotoxicity towards hypoxic tumour cells in vitro.使用彗星试验测量的替拉扎明诱导的DNA损伤与体外对缺氧肿瘤细胞的细胞毒性相关。
Br J Cancer. 1996 Apr;73(8):952-60. doi: 10.1038/bjc.1996.187.
4
Pre- and post-irradiation radiosensitization by SR 4233.SR 4233对辐射前后的放射增敏作用。
Int J Radiat Oncol Biol Phys. 1989 Apr;16(4):967-71. doi: 10.1016/0360-3016(89)90897-3.
5
Characterization of a CHO cell line resistant to killing by the hypoxic cell cytotoxin SR 4233.一种对缺氧细胞毒素SR 4233杀伤具有抗性的中国仓鼠卵巢细胞系的特性研究
Int J Radiat Oncol Biol Phys. 1992;22(4):681-4. doi: 10.1016/0360-3016(92)90502-9.
6
Reduction of 3-amino-1,2,4-benzotriazine-1,4-di-N-oxide (tirapazamine, WIN 59075, SR 4233) to a DNA-damaging species: a direct role for NADPH:cytochrome P450 oxidoreductase.3-氨基-1,2,4-苯并三嗪-1,4-二-N-氧化物（替拉扎明，WIN 59075，SR 4233）还原为一种DNA损伤物质：NADPH：细胞色素P450氧化还原酶的直接作用。
Carcinogenesis. 1994 Aug;15(8):1503-10. doi: 10.1093/carcin/15.8.1503.
7
Reductive metabolism of 3-amino-1,2,4-benzotriazine-1,4-dioxide (SR 4233) and the induction of unscheduled DNA synthesis in rat and human derived cell lines.3-氨基-1,2,4-苯并三嗪-1,4-二氧化物（SR 4233）的还原代谢以及在大鼠和人源细胞系中对非程序性DNA合成的诱导
Carcinogenesis. 1990 Aug;11(8):1407-11. doi: 10.1093/carcin/11.8.1407.
8
Metabolism of the bioreductive cytotoxin SR 4233 by tumour cells: enzymatic studies.肿瘤细胞对生物还原细胞毒素SR 4233的代谢：酶学研究
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9
Selective potentiation of the hypoxic cytotoxicity of tirapazamine by its 1-N-oxide metabolite SR 4317.替拉扎明的1-N-氧化物代谢物SR 4317对其缺氧细胞毒性的选择性增强作用。
Cancer Res. 2004 Jan 15;64(2):736-42. doi: 10.1158/0008-5472.can-03-2488.
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Homologous recombination repair-dependent cytotoxicity of the benzotriazine di-N-oxide CEN-209: comparison with other hypoxia-activated prodrugs.苯并三嗪二氮氧化物 CEN-209 的同源重组修复依赖性细胞毒性：与其他缺氧激活前药的比较。
Biochem Pharmacol. 2012 Mar 1;83(5):574-85. doi: 10.1016/j.bcp.2011.12.005. Epub 2011 Dec 13.

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Heterocyclic N-Oxides - An Emerging Class of Therapeutic Agents.杂环氮氧化物——一类新兴的治疗药物。
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DNA strand cleaving properties and hypoxia-selective cytotoxicity of 7-chloro-2-thienylcarbonyl-3-trifluoromethylquinoxaline 1,4-dioxide.7-氯-2-噻吩羰基-3-三氟甲基喹喔啉 1,4-二氧化物的 DNA 链断裂特性和缺氧选择性细胞毒性。
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DNA strand damage product analysis provides evidence that the tumor cell-specific cytotoxin tirapazamine produces hydroxyl radical and acts as a surrogate for O(2).DNA链损伤产物分析提供了证据，表明肿瘤细胞特异性细胞毒素替拉扎明可产生羟基自由基并作为O(2)的替代物发挥作用。
J Am Chem Soc. 2007 Oct 24;129(42):12870-7. doi: 10.1021/ja074432m. Epub 2007 Sep 27.
6
Does reductive metabolism predict response to tirapazamine (SR 4233) in human non-small-cell lung cancer cell lines?还原代谢能否预测人非小细胞肺癌细胞系对替拉扎明（SR 4233）的反应？
Br J Cancer. 1999 Dec;81(7):1127-33. doi: 10.1038/sj.bjc.6690819.
7
Tirapazamine-induced DNA damage measured using the comet assay correlates with cytotoxicity towards hypoxic tumour cells in vitro.使用彗星试验测量的替拉扎明诱导的DNA损伤与体外对缺氧肿瘤细胞的细胞毒性相关。
Br J Cancer. 1996 Apr;73(8):952-60. doi: 10.1038/bjc.1996.187.
8
SR 4233 (tirapazamine): a new anticancer drug exploiting hypoxia in solid tumours.SR 4233（替拉扎明）：一种利用实体瘤缺氧特性的新型抗癌药物。
Br J Cancer. 1993 Jun;67(6):1163-70. doi: 10.1038/bjc.1993.220.
9
Metabolism of the bioreductive cytotoxin SR 4233 by tumour cells: enzymatic studies.肿瘤细胞对生物还原细胞毒素SR 4233的代谢：酶学研究
Br J Cancer. 1993 Feb;67(2):321-5. doi: 10.1038/bjc.1993.59.
10
The experimental development of bioreductive drugs and their role in cancer therapy.生物还原药物的实验进展及其在癌症治疗中的作用。
Cancer Metastasis Rev. 1993 Jun;12(2):73-82. doi: 10.1007/BF00689802.

本文引用的文献

1
The histological structure of some human lung cancers and the possible implications for radiotherapy.一些人类肺癌的组织学结构及其对放射治疗的可能影响。
Br J Cancer. 1955 Dec;9(4):539-49. doi: 10.1038/bjc.1955.55.
2
Response of Chinese hamster ovary cells to anticancer drugs under aerobic and hypoxic conditions.中国仓鼠卵巢细胞在有氧和缺氧条件下对抗癌药物的反应。
Br J Cancer. 1981 Feb;43(2):245-8. doi: 10.1038/bjc.1981.37.
3
Enhancement of CCNU cytotoxicity by misonidazole: possible therapeutic gain.米索硝唑增强洛莫司汀的细胞毒性：可能的治疗获益。
Br J Cancer. 1982 Jul;46(1):109-16. doi: 10.1038/bjc.1982.172.
4
Isolation of cell cycle-dependent gamma ray-sensitive Chinese hamster ovary cell.细胞周期依赖性γ射线敏感的中国仓鼠卵巢细胞的分离
Somatic Cell Genet. 1983 Mar;9(2):165-73. doi: 10.1007/BF01543175.
5
On the nature of a defect in cells from individuals with ataxia-telangiectasia.关于共济失调毛细血管扩张症患者细胞中一种缺陷的本质。
Science. 1985 Mar 29;227(4694):1589-91. doi: 10.1126/science.3975628.
6
Identification of two major reduction products of the hypoxic cell toxin 3-amino-1,2,4-benzotriazine-1,4-dioxide.缺氧细胞毒素3-氨基-1,2,4-苯并三嗪-1,4-二氧化物两种主要还原产物的鉴定
Biochem Pharmacol. 1986 Oct 1;35(19):3417-20. doi: 10.1016/0006-2952(86)90448-x.
7
SR-4233: a new bioreductive agent with high selective toxicity for hypoxic mammalian cells.SR - 4233：一种对缺氧哺乳动物细胞具有高选择性毒性的新型生物还原剂。
Int J Radiat Oncol Biol Phys. 1986 Jul;12(7):1239-42. doi: 10.1016/0360-3016(86)90267-1.
8
Enhancement of radiation-induced tumor cell killing by the hypoxic cell toxin SR 4233.低氧细胞毒素SR 4233增强辐射诱导的肿瘤细胞杀伤作用。
Radiother Oncol. 1988 Jul;12(3):209-18. doi: 10.1016/0167-8140(88)90263-0.
9
Metabolism of SR 4233 by Chinese hamster ovary cells: basis of selective hypoxic cytotoxicity.
Cancer Res. 1988 Nov 1;48(21):5947-52.
10
Molecular mechanisms for the hypoxia-dependent activation of 3-amino-1,2,4-benzotriazine-1,4-dioxide (SR 4233).
Biochem Pharmacol. 1988 Apr 15;37(8):1487-95. doi: 10.1016/0006-2952(88)90010-x.

SR 4233在具备DNA修复能力和缺乏DNA修复能力的细胞培养物中的细胞毒性及代谢情况。

SR 4233 cytotoxicity and metabolism in DNA repair-competent and repair-deficient cell cultures.

作者信息

Biedermann K A, Wang J, Graham R P, Brown J M

机构信息

Department of Radiation Oncology, Stanford University School of Medicine, California 94305.

出版信息

Br J Cancer. 1991 Mar;63(3):358-62. doi: 10.1038/bjc.1991.85.

DOI:10.1038/bjc.1991.85
PMID:2003976
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1971850/
Abstract

In order to understand in more detail the mechanism underlying the preferential hypoxic cytotoxicity of the benzotriazine N-oxide SR 4233, we have compared the hypoxic cytotoxicity of this drug to the rates of hypoxic metabolism in both DNA double strand break repair-competent and repair-deficient cell cultures. Rodent SCCVII cells and repair deficient, radiation sensitive cells (rodent XR-1, V-3, and human AT5BI) were most sensitive to SR 4233 under hypoxia with a lethal dose needed to kill 50% of cells (LD50) of less than 5 microM. SR 4233 was less cytotoxic to human AG 1522 (LD50 = 18 microM), CHO 4364 (LD50 = 25 microM) and human HT 1080 cells (LD50 = 33 microM). The sensitivities to SR 4233 were found to be inversely proportional to the rates of SR 4233 metabolism in repair-competent cells (R2 = 0.9). However, XR-1 and V-3 cells were more sensitive to SR 4233 than predicted by the metabolism rate. Thus, the toxicity by SR 4233 towards hypoxic cells appears to result from two mechanisms; the rate of drug metabolism and the ability to repair DNA double strand breaks.

摘要

为了更详细地了解苯并三嗪氮氧化物SR 4233优先产生缺氧细胞毒性的潜在机制，我们比较了该药物在DNA双链断裂修复能力正常和修复缺陷的细胞培养物中的缺氧细胞毒性与缺氧代谢率。啮齿动物SCCVII细胞以及修复缺陷、对辐射敏感的细胞（啮齿动物XR-1、V-3和人类AT5BI）在缺氧条件下对SR 4233最为敏感，杀死50%细胞所需的致死剂量（LD50）小于5微摩尔。SR 4233对人类AG 1522（LD50 = 18微摩尔）、CHO 4364（LD50 = 25微摩尔）和人类HT 1080细胞（LD50 = 33微摩尔）的细胞毒性较小。发现对SR 4233的敏感性与修复能力正常的细胞中SR 4233的代谢率成反比（R2 = 0.9）。然而，XR-1和V-3细胞对SR 4233的敏感性比根据代谢率预测的更高。因此，SR 4233对缺氧细胞的毒性似乎源于两种机制；药物代谢率和修复DNA双链断裂的能力。