Protection against radiation-induced degradation of DNA bases by polyamines.
Polyamines have been reported to protect DNA against the formation of radiation-induced strand breaks and crosslinks to proteins. The present study was aimed at investigating the protective effect of spermine, spermidine and putrescine against the degradation of DNA bases upon exposure to gamma rays in aerated aqueous solution. The yield of 8-oxo-7,8-dihydroguanine and 5-hydroxycytosine was found to decrease for concentrations of spermine and spermidine greater than 0.1 mM. A protection factor of 10 was observed for a concentration of 1 mM of the latter two polyamines. Putrescine afforded a lower protection. In addition, the formation yield of a series of radiation-induced degradation products of the purine and pyrimidine bases was determined within DNA in the presence or absence of spermine. The protection factor was within the same range for all the lesions measured. The latter observation ruled out the possibility of degradation of DNA by radiation-induced polyamine peroxyl radicals. This was confirmed by studies involving radiolysis of DMSO and decomposition of 2,2'-azobis(2-methyl-propionamidine) as sources of alkylperoxyl radicals. Therefore, it is likely that the polyamine-mediated protection against the radiation-induced degradation of DNA bases is due to the compaction of the DNA structure and the reduction in the accessibility of DNA to .OH rather than by scavenging .OH in the bulk solution or in the vicinity of the DNA.
Douki
T
T
Laboratoire des Lésions des Acides Nucléiques, Service de Chimie Inorganique et Biologique, Département de Recherche Fondamentale sur la Matière Condensée, CEA/Grenoble, 17 Avenue des Martyrs, 38054 Grenoble Cedex 9, France.
Bretonniere
Y
Y
Cadet
J
J
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000578:Amidines / Q000494:pharmacology; D003596:Cytosine / Q000031:analogs & derivatives / Q000032:analysis / Q000138:chemical synthesis; D004247:DNA / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects; D004249:DNA Damage / Q000187:drug effects*; D003839:Deoxyadenosines / Q000378:metabolism / Q000528:radiation effects; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000032:analysis / Q000138:chemical synthesis; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis / Q000138:chemical synthesis; D004121:Dimethyl Sulfoxide / Q000378:metabolism / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D005720:Gamma Rays; D008401:Gas Chromatography-Mass Spectrometry; D006147:Guanine / Q000031:analogs & derivatives / Q000032:analysis / Q000138:chemical synthesis; D017665:Hydroxyl Radical / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D011073:Polyamines / Q000494:pharmacology*; D011687:Purines / Q000737:chemistry / Q000528:radiation effects*; D011700:Putrescine / Q000494:pharmacology; D011743:Pyrimidines / Q000737:chemistry / Q000528:radiation effects*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D012996:Solutions; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology
D000578:Amidines; D003839:Deoxyadenosines; D011073:Polyamines; D011687:Purines; D011743:Pyrimidines; D011837:Radiation-Protective Agents; D012996:Solutions; D003841:Deoxycytidine; D013096:Spermine; D017665:Hydroxyl Radical; C074071:5-hydroxy-2'-deoxycytidine; C024829:8-hydroxyguanine; D006147:Guanine; C046728:2,2'-azobis(2-amidinopropane); C017400:5-hydroxycytosine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003596:Cytosine; D004247:DNA; D003849:Deoxyguanosine; D013095:Spermidine; D011700:Putrescine; D004121:Dimethyl Sulfoxide