No correlation between germline mutation at repeat DNA and meiotic crossover in male mice exposed to X-rays or cisplatin.
To test the hypothesis that mouse germline expanded simple tandem repeat (ESTR) mutations are associated with recombination events during spermatogenesis, crossover frequencies were compared with germline mutation rates at ESTR loci in male mice acutely exposed to 1Gy of X-rays or to 10mg/kg of the anticancer drug cisplatin. Ionising radiation resulted in a highly significant 2.7-3.6-fold increase in ESTR mutation rate in males mated 4, 5 and 6 weeks after exposure, but not 3 weeks after exposure. In contrast, irradiation had no effect on meiotic crossover frequencies assayed on six chromosomes using 25 polymorphic microsatellite loci spaced at approximately 20cM intervals and covering 421cM of the mouse genome. Paternal exposure to cisplatin did not affect either ESTR mutation rates or crossover frequencies, despite a report that cisplatin can increase crossover frequency in mice. Correlation analysis did not reveal any associations between the paternal ESTR mutation rate and crossover frequency in unexposed males and in those exposed to X-rays or cisplatin. This study does not, therefore, support the hypothesis that mutation induction at mouse ESTR loci results from a general genome-wide increase in meiotic recombination rate.
Barber
R
R
Department of Genetics, University of Leicester, LE1 7RH, Leicester, UK.
Plumb
M
M
Smith
A G
AG
Cesar
C E
CE
Boulton
E
E
Jeffreys
A J
AJ
Dubrova
Y E
YE
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D002945:Cisplatin / Q000633:toxicity; D003432:Cross-Linking Reagents / Q000633:toxicity; D003434:Crossing Over, Genetic / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D004247:DNA / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D018095:Germ-Line Mutation; D008297:Male; D008540:Meiosis / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D013091:Spermatogenesis / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D020080:Tandem Repeat Sequences
D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D004247:DNA; D002945:Cisplatin