Amifostine induces antioxidant enzymatic activities in normal tissues and a transplantable tumor that can affect radiation response.
Amifostine induces antioxidant enzymatic activities in normal tissues and a transplantable tumor that can affect radiation response.
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氨磷汀可在正常组织和可移植肿瘤中诱导抗氧化酶活性，从而影响放射反应。
DOI：
10.1016/j.ijrobp.2008.10.061
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发表时间：
2009-03-01
影响因子：
7
通讯作者：
Spitz, Douglas R.
中科院分区：
文献类型：
--
作者：
Grdina, David J.;Murley, Jeffrey S.;Kataoka, Yasushi;Baker, Kenneth L.;Kunnavakkam, Rangesh;Coleman, Mitchell C.;Spitz, Douglas R.
本研究的目的是确定氨磷汀是否可以诱导小鼠组织中锰超氧化物歧化酶（SOD 2）升高，并导致延迟肿瘤细胞辐射保护作用的可移植SA-NH肿瘤。SA-NH荷瘤C3 H小鼠用单次400 mg/kg或每日三次50 mg/kg剂量的氨磷汀腹膜内给药治疗。在最后一次注射后的选定时间间隔，取出心脏、肝脏、肺、胰腺、小肠、脾脏和SA-NH肿瘤，并分析SOD 2、过氧化氢酶和谷胱甘肽过氧化物酶（GPx）酶活性。测定了SOD 2酶活性升高对SA-NH细胞辐射反应的影响。氨磷汀治疗后24小时，选定的组织和肿瘤中SOD 2活性显著升高。过氧化氢酶和GPx活动保持不变，但显着升高，在脾脏。GPx在胰腺中也升高。SA-NH肿瘤细胞表现出2倍的SOD 2活性升高和27%的辐射抗性升高。氨磷汀每天分3次给药，每次50 mg/kg，也导致这些抗氧化酶显著升高。氨磷汀可诱导SA-NH肿瘤的延迟辐射保护作用，其与升高的SOD 2活性水平相关。如果仅限于正常组织，这种延迟的辐射防护作用为整体辐射防护提供了额外的潜力。然而，阿米福汀诱导的肿瘤中SOD 2活性升高可能对肿瘤对分次放射治疗的反应产生意外的有害影响，因为放射保护剂每天在每次2戈伊分次剂量之前施用。
The purpose of this study is to determine whether amifostine can induce elevated manganese superoxide dismutase (SOD2) in mouse tissues and a transplantable SA-NH tumor resulting in a delayed tumor cell radioprotective effect. SA-NH tumor-bearing C3H mice were treated with a single 400 mg/kg or three daily 50 mg/kg doses of amifostine administered i.p. At selected time intervals following the last injection, heart, liver, lung, pancreas, small intestine, spleen and SA-NH tumor were removed and analyzed for SOD2, catalase, and glutathione peroxidase (GPx) enzymatic activity. The effect of elevated SOD2 enzymatic activity on the radiation response of SA-NH cells was determined. SOD2 activity was significantly elevated in selected tissues and a tumor 24 h following amifostine treatment. Catalase and GPx activities remained unchanged except for significant elevations in the spleen. GPx was also elevated in the pancreas. SA-NH tumor cells exhibited a 2-fold elevation in SOD2 activity and a 27% elevation in radiation resistance. Amifostine administered in 3 daily fractions of 50 mg/kg each also resulted in significant elevations of these anti-oxidant enzymes. Amifostine can induce a delayed radioprotective effect that correlates with elevated levels of SOD2 activity in SA-NH tumor. If limited to normal tissues, this delayed radioprotective effect offers an additional potential for overall radiation protection. However, amifostine-induced elevation of SOD2 activity in tumors could have an unanticipated deleterious effect on tumor responses to fractionated radiation therapy given that the radioprotector is administered daily just prior to each 2 Gy fractionated dose.
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影响因子：
45.3
作者：
Brizel, DM;Wasserman, TH;Sauer, R
通讯作者：
Sauer, R
DOI：
10.1152/ajplung.1995.269.5.l588
发表时间：
1995-11-01
影响因子：
4.9
作者：
DAS, KC;LEWISMOLOCK, Y;WHITE, CW
通讯作者：
WHITE, CW
影响因子：
3.4
作者：
Epperly, MW;Gretton, JE;Greenberger, JS
通讯作者：
Greenberger, JS
影响因子：
5.3
作者：
Guo, GZ;Yan-Sanders, Y;Li, JJ
通讯作者：
Li, JJ
DOI：
10.1016/0006-291x(76)90747-6
发表时间：
1976-01-01
影响因子：
3.1
作者：
LAWRENCE, RA;BURK, RF
通讯作者：
BURK, RF