* Department of Genetics, University of Leicester, Leicester LE1
7RH, United Kingdom; and Edited by Richard B. Setlow, Brookhaven National Laboratory,
Upton, NY, and approved March 26, 2002 (received for review January 9, 2002)
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.
Genetics
Elevated mutation rates in the germ line of first- and
second-generation offspring of irradiated male mice
,
Medical Research Council
Radiation and Genome Stability Unit, Harwell, Oxon OX11 0RD, United
Kingdom
To whom reprint requests should be addressed.
E-mail: yed2{at}le.ac.uk.
www.pnas.org/cgi/doi/10.1073/pnas.102015399
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