Elevated mutation rates in the germ line of first- and second-generation offspring of irradiated male mice.
Mutation rates at two expanded simple tandem repeat loci were studied in the germ line of first- and second-generation offspring of inbred male CBA/H, C57BL/6, and BALB/c mice exposed to either high linear energy transfer fission neutrons or low linear energy transfer x-rays. Paternal CBA/H exposure to either x-rays or fission neutrons resulted in increased mutation rates in the germ line of two subsequent generations. Comparable transgenerational effects were observed also in neutron-irradiated C57BL/6 and x-irradiated BALB/c mice. The levels of spontaneous mutation rates and radiation-induced transgenerational instability varied between strains (BALB/c>CBA/H>C57BL/6). Pre- and postmeiotic paternal exposure resulted in similar increases in mutation rate in the germ line of both generations of CBA/H mice, which together with our previous results suggests that radiation-induced expanded simple tandem repeat instability is manifested in diploid cells after fertilization. The remarkable finding that radiation-induced germ-line instability persists for at least two generations raises important issues of risk evaluation in humans.
Barber
Ruth
R
Department of Genetics, University of Leicester, Leicester LE1 7RH, United Kingdom.
Plumb
Mark A
MA
Boulton
Emma
E
Roux
Isabelle
I
Dubrova
Yuri E
YE
D000483:Alleles; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D004735:Energy Transfer; D005260:Female; D018095:Germ-Line Mutation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010375:Pedigree; D012107:Research Design; D013094:Spermatozoa; D020080:Tandem Repeat Sequences; D014916:Whole-Body Irradiation
D019941:Cyclin-Dependent Kinase Inhibitor p16; D017868:Cyclic AMP-Dependent Protein Kinases