Ongoing Y-chromosome instability defines sub-clonal variants in radiation-induced leukaemias in the mouse.
Forty primary leukaemias that arose in vivo as a consequence of 3 Gy X-irradiation of inbred mouse strains were analysed for Y-chromosome aberrations by conventional cytogenetics and fluorescent in situ hybridization (FISH). Compared with control mice which were X-irradiated but which exhibited no overt signs of leukaemia, the loss and gain of Y-chromosomes in leukaemic spleen cells defined subclonal variants in the radiation-induced haemopoietic malignancies that arose in CBA/H, DBA/2 and (C57BL/6 x DBA/2)F1 mice. This Y-chromosome instability was significantly higher than that observed in spleen cells of age-matched (or older) irradiated control mice that had not developed overt leukaemia. The detection of Y-chromosome aberrations is considered in the context of the high numbers of potential gene regulatory sequences in the murine Y-chromosome and the potential for the insertional activation of cellular genes during multi-stage radiation leukaemogenesis.
Plumb
M
M
MRC Radiation and Genetic Stability Unit, Chilton, Didcot, U.K.
Harper
K
K
MacDonald
D
D
Fennelly
J
J
Lorimore
S
S
Wright
E
E
D000208:Acute Disease; D000818:Animals; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002999:Clone Cells; D017404:In Situ Hybridization, Fluorescence; D007951:Leukemia, Myeloid / Q000209:etiology / Q000235:genetics*; D007953:Leukemia, Radiation-Induced / Q000235:genetics*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D014998:Y Chromosome / Q000528:radiation effects*