Minisatellite mutation frequency in human sperm following radiotherapy

被引:39
作者
May, CA
Tamaki, K
Neumann, R
Wilson, G
Zagars, G
Pollack, A
Dubrova, YE
Jeffreys, AJ
Meistrich, ML
机构
[1] Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England
[2] Univ Texas, MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA
[3] Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA
基金
美国国家卫生研究院; 英国惠康基金; 英国医学研究理事会;
关键词
minisatellite; sperm; germline mutation; radiotherapy; ionizing radiation;
D O I
10.1016/S0027-5107(00)00085-3
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Screening pedigrees for inherited minisatellite length changes provides an efficient means of monitoring repeat DNA instability but has given rise to apparently contradictory results regarding the effects of radiation on the human germline. To explore this further in individuals with known radiation doses and to potentially gain information on the timing of mutation induction, we have used an extremely sensitive single molecule approach to quantify the frequencies of mutation at the hypervariable minisatellites B6.7 and CEB1 in the sperm of three seminoma patients following hemipelvic radiotherapy. Scattered radiation doses to the testicles were monitored and pre-treatment sperm DNA was compared with sperm derived from irradiated pre-meiotic, meiotic and post-meiotic cells. We show no evidence for mutation induction in any of the patients and discuss this finding in the context of previous population studies using minisatellites as reporter systems, one of which provided evidence for radiation-induced germline mutation. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:67 / 75
页数:9
相关论文
共 36 条
[21]   Repeat instability at human minisatellites arising from meiotic recombination [J].
Jeffreys, AJ ;
Neil, DL ;
Neumann, R .
EMBO JOURNAL, 1998, 17 (14) :4147-4157
[22]   SPONTANEOUS MUTATION-RATES TO NEW LENGTH ALLELES AT TANDEM-REPETITIVE HYPERVARIABLE LOCI IN HUMAN DNA [J].
JEFFREYS, AJ ;
ROYLE, NJ ;
WILSON, V ;
WONG, Z .
NATURE, 1988, 332 (6161) :278-281
[23]   REPEAT UNIT SEQUENCE VARIATION IN MINISATELLITES - A NOVEL SOURCE OF DNA POLYMORPHISM FOR STUDYING VARIATION AND MUTATION BY SINGLE MOLECULE ANALYSIS [J].
JEFFREYS, AJ ;
NEUMANN, R ;
WILSON, V .
CELL, 1990, 60 (03) :473-485
[24]   CHARACTERIZATION OF A HIGHLY UNSTABLE MOUSE MINISATELLITE LOCUS - EVIDENCE FOR SOMATIC MUTATION DURING EARLY DEVELOPMENT [J].
KELLY, R ;
BULFIELD, G ;
COLLICK, A ;
GIBBS, M ;
JEFFREYS, AJ .
GENOMICS, 1989, 5 (04) :844-856
[25]  
KIMPTON CP, 1992, ADV FORENSIC HAEMOGE, V4, P129
[26]  
KODAIRA M, 1995, AM J HUM GENET, V57, P1275
[27]  
Livshits LA, 1999, INT J RAD MED, V1, P101
[28]   A COMPARISON OF CHROMOSOMAL-ABERRATIONS INDUCED BY INVIVO RADIOTHERAPY IN HUMAN-SPERM AND LYMPHOCYTES [J].
MARTIN, RH ;
RADEMAKER, A ;
HILDEBRAND, K ;
BARNES, M ;
ARTHUR, K ;
RINGROSE, T ;
BROWN, IS ;
DOUGLAS, G .
MUTATION RESEARCH, 1989, 226 (01) :21-30
[29]   Mutation rate heterogeneity and the generation of allele diversity at the human minisatellite MS205 (D16S309) [J].
May, CA ;
Jeffreys, AJ ;
Armour, JAL .
HUMAN MOLECULAR GENETICS, 1996, 5 (11) :1823-1833
[30]   Hormonal stimulation of the recovery of spermatogenesis following chemo- or radiotherapy - Review article [J].
Meistrich, ML .
APMIS, 1998, 106 (01) :37-45