Radioprotection against the formation of DNA double-strand breaks in cellular DNA but not native cellular chromatin by the polyamine spermine

被引:22
作者
Chiu, SM
Oleinick, NL
机构
[1] Division of Radiation Biology, Department of Radiology, Case W. Reserve Univ. Sch. of Med., Cleveland
[2] Division of Radiation Biology, School of Medicine (BRB), Case Western Reserve University, Cleveland, OH 44106-4942
关键词
D O I
10.2307/3579577
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The complexing of histones with DNA and the resulting condensation of chromatin protect mammalian cell DNA from radiation-induced strand breakage. In recent studies of SV40 DNA and minichromosomes, marked radioprotection was afforded by spermine through polyamine-induced compaction and aggregation (Newton et at, Radiat. Res. 145, 776-780, 1996). To evaluate the contribution of polyamines to the radioprotection of cellular chromatin, intact V79 cells, nuclei (native chromatin) and chromatin that was partially or completely stripped of histones were treated with spermine or putrescine and gamma-irradiated while embedded in agarose plugs, and induction of double-strand breaks was determined by pulsed-field gel electrophoresis. In the absence of added spermine, the order of radiosensitivity was: dehistonized chromatin (DNA loops anchored to the nuclear matrix) > chromatin depleted of histone H1 > chromatin partially depleted of histone H1 > native chromatin > intact cells. Spermine at concentrations below 1 mM was without effect on strand breakage in any of the preparations, except for limited radioprotection of H1-depleted chromatin. Increasing radioprotection with increasing concentration (1-10 mM) was provided to dehistonized chromatin by spermine but not by putrescine, a polyamine that does not compact DNA or chromatin. Significant radioprotection by spermine was also found for HI-depleted relaxed chromatin at concentrations greater than or equal to 1 mM. In contrast, no radioprotection by spermine (up to 10 mM) was observed for any of the chromatin preparations containing all histones. These observations support the hypothesis proposed by Newton et al. that spermine protects DNA against radiation damage via polyamine-induced compaction and aggregation. With removal of histone HI, the exposed chromatin develops the ability to be protected by spermine. However, the absence of radioprotection of native chromatin by spermine is consistent with a role for histones as the major radioprotectors of cellular DNA and the differential radiosensitivity of decondensed compared to condensed cellular chromatin resulting from the effects of factors other than polyamines. (C) 1997 by Radiation Research Society.
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页码:188 / 192
页数:5
相关论文
共 20 条
[1]   ELECTROSTATIC MECHANISM OF NUCLEOSOME SPACING [J].
BLANK, TA ;
BECKER, PB .
JOURNAL OF MOLECULAR BIOLOGY, 1995, 252 (03) :305-313
[2]   THE FOLDING OF CHROMATIN [J].
BUTLER, PJG .
CRC CRITICAL REVIEWS IN BIOCHEMISTRY, 1983, 15 (01) :57-91
[3]   DNA CONDENSATION WITH POLYAMINES .2. ELECTRON-MICROSCOPIC STUDIES [J].
CHATTORAJ, DK ;
GOSULE, LC ;
SCHELLMAN, JA .
JOURNAL OF MOLECULAR BIOLOGY, 1978, 121 (03) :327-337
[4]  
ELIA MC, 1992, CANCER RES, V52, P1580
[5]   RADIOLYTIC FOOTPRINTING - BETA-RAYS, GAMMA-PHOTONS, AND FAST-NEUTRONS PROBE DNA-PROTEIN INTERACTIONS [J].
FRANCHETBEUZIT, J ;
SPOTHEIMMAURIZOT, M ;
SABATTIER, R ;
BLAZYBAUDRAS, B ;
CHARLIER, M .
BIOCHEMISTRY, 1993, 32 (08) :2104-2110
[6]   CONDENSATION AND PRECIPITATION OF CHROMATIN BY MULTIVALENT CATIONS [J].
FREDERICQ, E ;
HACHA, R ;
COLSON, P ;
HOUSSIER, C .
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 1991, 8 (04) :847-865
[7]   DNA CONDENSATION WITH POLYAMINES .1. SPECTROSCOPIC STUDIES [J].
GOSULE, LC ;
SCHELLMAN, JA .
JOURNAL OF MOLECULAR BIOLOGY, 1978, 121 (03) :311-326
[8]   EFFECTS OF POLYAMINES AND THIOLS ON THE RADIATION SENSITIVITY OF BACTERIAL TRANSFORMING DNA [J].
HELD, KD ;
AWAD, S .
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 1991, 59 (03) :699-710
[9]   RADIOPROTECTION OF DNA BY A DNA-BINDING PROTEIN - MC1 CHROMOSOMAL PROTEIN FROM THE ARCHAEBACTERIUM METHANOSARCINA SP CHTI55 [J].
ISABELLE, V ;
FRANCHETBEUZIT, J ;
SABATTIER, R ;
LAINE, B ;
SPOTHEIMMAURIZOT, M ;
CHARLIER, M .
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 1993, 63 (06) :749-758
[10]   BIOCHEMICAL AND ULTRASTRUCTURAL ANALYSIS OF SV40-CHROMATIN [J].
KELLER, W ;
MULLER, U ;
EICKEN, I ;
WENDEL, I ;
ZENTGRAF, H .
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY, 1977, 42 :227-244