Persistent induction of somatic reversions of the pink-eyed unstable mutation in F1 mice born to fathers irradiated at the spermatozoa stage.
Untargeted mutation and delayed mutation are features of radiation-induced genomic instability and have been studied extensively in tissue culture cells. The mouse pink-eyed unstable (p(un)) mutation is due to an intragenic duplication of the pink-eyed dilution locus and frequently reverts back to the wild type in germ cells as well as in somatic cells. The reversion event can be detected in the retinal pigment epithelium as a cluster of pigmented cells (eye spot). We have investigated the reversion p(um) in F1 mice born to irradiated males. Spermatogonia-stage irradiation did not affect the frequency of the reversion in F1 mice. However, 6 Gy irradiation at the spermatozoa stage resulted in an approximately twofold increase in the number of eye spots in the retinal pigment epithelium of F1 mice. Somatic reversion occurred for the paternally derived p(un) alleles. In addition, the reversion also occurred for the maternally derived, unirradiated p(un) alleles at a frequency equal to that for the paternally derived allele. Detailed analyses of the number of pigmented cells per eye spot indicated that the frequency of reversion was persistently elevated during the proliferation cycle of the cells in the retinal pigment epithelium when the male parents were irradiated at the spermatozoa stage. The present study demonstrates the presence of a long-lasting memory of DNA damage and the persistent up-regulation of recombinogenic activity in the retinal pigment epithelium of the developing fetus.
Shiraishi
Kazunori
K
Department of Late Effect Studies, Radiation Biology Center, Kyoto University, Yoshida Konoe, Sakyo-ku, Kyoto 606-8501, Japan.
Shimura
Tsutomu
T
Taga
Masataka
M
Uematsu
Norio
N
Gondo
Yoichi
Y
Ohtaki
Megu
M
Kominami
Ryo
R
Niwa
Ohtsura
O
D000818:Animals; D002352:Carrier Proteins; D003433:Crosses, Genetic; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects*; D005314:Embryonic and Fetal Development / Q000528:radiation effects; D005123:Eye / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics* / Q000528:radiation effects; D010641:Phenotype; D010857:Pigment Epithelium of Eye / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D013094:Spermatozoa / Q000378:metabolism / Q000528:radiation effects*; D013489:Suppression, Genetic / Q000235:genetics / Q000528:radiation effects
D002352:Carrier Proteins; D008565:Membrane Proteins; C076239:P protein, mouse