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 (E STR) mutations are associated with recombination events during spermatogene sis, crossover frequencies were compared with germline mutation rates at ES TR loci in male mice acutely exposed to 1 Gy of X-rays or to 10 mg/kg of th e anticancer drug cisplatin. Ionising radiation resulted in a highly signif icant 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, irradia tion had no effect on meiotic crossover frequencies assayed on six chromoso mes using 25 polymorphic microsatellite loci spaced at approximately 20 cM intervals and covering 421 cM of the mouse genome. Paternal exposure to cis platin 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 E STR mutation rate and crossover frequency in unexposed males and in those e xposed to X-rays or cisplatin. This study does not, therefore, support the hypothesis that mutation induction at mouse ESTR loci results from a genera l genome-wide increase in meiotic recombination rate. (C) 2000 Elsevier Sci ence B.V. All rights reserved.