DIFFERENTIAL REPAIR OF RADIATION-INDUCED DNA-DAMAGE IN CELLS OF HUMAN SQUAMOUS-CELL CARCINOMA AND THE EFFECT OF CAFFEINE AND CYSTEAMINE ON INDUCTION AND REPAIR OF DNA DOUBLE-STRAND BREAKS

被引:26
作者
SMEETS, MFMA [1 ]
MOOREN, EHM [1 ]
ABDELWAHAB, AHA [1 ]
BARTELINK, H [1 ]
BEGG, AC [1 ]
机构
[1] NETHERLANDS CANC INST,DIV EXPTL THERAPY,1066 CX AMSTERDAM,NETHERLANDS
关键词
D O I
10.2307/3578897
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The goal of these experiments was to investigate further the relationship between DNA double-strand breaks and cell killing in human tumor cells, first by comparing different cell lines, and second by radiomodification studies. Field-inversion gel electrophoresis was used to quantify double-strand breaks. Two subclones of the radioresistant human squamous cell carcinoma line SQ20B (SQD9 and SQG6) were compared. These subclones differed in DNA index by a factor of 1.7 but showed the same resistance to radiation as cells of the parental cell line. It was found that, although induction of DSBs was not significantly different in the two cell lines, the t(1/2) of the fast component of repair was significantly shorter for SQD9 cells, leading to greater overall repair which was not reflected in increased survival. Caffeine and cysteamine were tested as modifiers of radiosensitivity, using the radioresistant SQ20B line and the radiosensitive SCC61 cell line. No effect of caffeine was seen when the drug was present only during irradiation. Postirradiation incubations with caffeine, however, resulted in a dose reduction factor greater than 2.0 in cell survival for both cell lines. In contrast, induction of DSBs was reduced by caffeine, and no effect on DSB repair was observed. Cysteamine led to a dose protection factor greater than 1.8 in cell survival in both cell lines. A reduction in induced DSBs was found at high doses corresponding approximately with the increase in cell survival. Over the same (low) dose range, however, the correlation between DSB induction and cell killing was poor. These data indicate that DSB induction does not correlate well with cell killing either for different cell lines, for radiochemical modification (cysteamine) or for some other types of modification (caffeine).
引用
收藏
页码:153 / 160
页数:8
相关论文
共 31 条
[1]   CELL KINETIC-ANALYSIS OF MIXED POPULATIONS USING 3-COLOR FLUORESCENCE FLOW-CYTOMETRY [J].
BEGG, AC ;
HOFLAND, I .
CYTOMETRY, 1991, 12 (05) :445-454
[2]  
BROWN JM, 1992, INT J RADIAT ONCOL, V24, P279, DOI 10.1016/0360-3016(92)90682-8
[3]   RADIOPROTECTION OF DNA IN ISOLATED-NUCLEI BY NATURALLY-OCCURRING THIOLS AT INTERMEDIATE OXYGEN-TENSION [J].
BUMP, EA ;
CERCE, BA ;
ALSARRAF, R ;
PIERCE, SM ;
KOCH, CJ .
RADIATION RESEARCH, 1992, 132 (01) :94-104
[4]   REPAIRABLE AND NONREPAIRABLE DNA STRAND BREAKS INDUCED BY X-IRRADIATION IN CHO K1 CELLS AND THE RADIOSENSITIVE MUTANTS XRS1 AND XRS5 [J].
DAHMDAPHI, J ;
DIKOMEY, E ;
PYTTLIK, C ;
JEGGO, PA .
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 1993, 64 (01) :19-26
[5]   DNA DOUBLE-STRAND BREAK REJOINING DEFICIENCY IN TK6 AND OTHER HUMAN B-LYMPHOBLAST CELL-LINES [J].
EVANS, HH ;
RICANATI, M ;
HORNG, MF ;
JIANG, QY ;
MENCL, J ;
OLIVE, P .
RADIATION RESEARCH, 1993, 134 (03) :307-315
[6]   USE OF PULSED-FIELD GEL-ELECTROPHORESIS TO MEASURE X-RAY-INDUCED DOUBLE-STRAND BREAKS IN DNA SUBSTITUTED WITH BRDU [J].
GARWOOD, DP ;
THOMPSON, LL ;
DEWEY, WC .
RADIATION RESEARCH, 1991, 128 (02) :210-215
[7]   THE USE OF ASYMMETRIC-FIELD INVERSION GEL-ELECTROPHORESIS TO PREDICT TUMOR-CELL RADIOSENSITIVITY [J].
GIACCIA, AJ ;
SCHWARTZ, J ;
SHIEH, J ;
BROWN, JM .
RADIOTHERAPY AND ONCOLOGY, 1992, 24 (04) :231-238
[8]  
ILIAKIS GE, 1991, CANCER RES, V50, P6575
[9]   INDUCTION AND REJOINING OF DNA DOUBLE-STRAND BREAKS IN HUMAN CERVIX CARCINOMA CELL-LINES OF DIFFERING RADIOSENSITIVITY [J].
KELLAND, LR ;
EDWARDS, SM ;
STEEL, GG .
RADIATION RESEARCH, 1988, 116 (03) :526-538
[10]   RELATIVE CONTRIBUTIONS OF LEVELS OF INITIAL DNA-DAMAGE AND REPAIR OF DOUBLE-STRAND BREAKS TO THE IONIZING RADIATION-SENSITIVE PHENOTYPE OF THE CHINESE-HAMSTER CELL MUTANT, XR-V15B .1. X-RAYS [J].
KYSELA, BP ;
MICHAEL, BD ;
ARRAND, JE .
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 1993, 63 (05) :609-616