Abstract:
:The nitroxide Tempol, a stable free radical, has recently been shown to protect mammalian cells against several forms of oxidative stress including radiation-induced cytotoxicity. To extend this observation, six additional water-soluble nitroxides with different structural features were evaluated for potential radioprotective properties using Chinese hamster V79 cells and clonogenic assays. Nitroxides (10 mM) were added 10 min prior to radiation exposure and full radiation dose-response curves were determined. In addition to Tempol, five of the six nitroxides afforded in vitro radioprotection. The best protectors were found to be the positively charged nitroxides, Tempamine and 3-aminomethyl-PROXYL, with protection factors of 2.3 and 2.4, respectively, compared with Tempol, which had a protection factor of 1.3. 3-Carboxy-PROXYL, a negatively charged nitroxide, provided minimal protection. DNA binding characteristics as studied by nonequilibrium dialysis of DNA with each of the nitroxides demonstrated that Tempamine and 3-amino-methyl-PROXYL bound more strongly to DNA than did Tempol. Since DNA is assumed to be the target of radiation-induced cytotoxicity, differences in protection may be explained by variabilities in affinity of the protector for the target. This study establishes nitroxides as a general class of new nonthiol radioprotectors and suggests other parameters that may be exploited to find even better nitroxide-induced radioprotection.
journal_name
Radiat Resjournal_title
Radiation researchauthors
Hahn SM,Wilson L,Krishna CM,Liebmann J,DeGraff W,Gamson J,Samuni A,Venzon D,Mitchell JBsubject
Has Abstractpub_date
1992-10-01 00:00:00pages
87-93issue
1eissn
0033-7587issn
1938-5404journal_volume
132pub_type
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更新日期:1990-08-01 00:00:00
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更新日期:1990-05-01 00:00:00
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journal_title:Radiation research
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journal_title:Radiation research
pub_type: 杂志文章
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更新日期:1991-04-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1995-08-01 00:00:00
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更新日期:1986-10-01 00:00:00
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更新日期:1999-12-01 00:00:00
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pub_type: 杂志文章
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journal_title:Radiation research
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