Clonally expanded T-cell populations in atomic bomb survivors do not show excess levels of chromosome instability.
Radiation-induced genomic instability has been studied primarily in cultured cells, while in vivo studies have been limited. One major obstacle for in vivo studies is the lack of reliable biomarkers that are capable of distinguishing genetic alterations induced by delayed radiation effects from those that are induced immediately after a radiation exposure. Here we describe a method to estimate cytogenetic instability in vivo using chromosomally marked clonal T-cell populations in atomic bomb survivors. The basic idea is that clonal translocations are derived from single progenitor cells that acquired an aberration, most likely after a radiation exposure, and then multiplied extensively in vivo, resulting in a large number of progeny cells that eventually comprise several percent of the total lymphocyte population. Therefore, if chromosome instability began to operate soon after a radiation exposure, an elevated frequency of additional but solitary chromosome aberrations in clonal cell populations would be expected. In the present study, six additional translocations were found among 936 clonal cells examined with the G-band method (0.6%); the corresponding value with multicolor FISH analysis was 1.2% (4/333). Since these frequencies were no higher than 1.2% (219/17,878 cells), the mean translocation frequency observed in control subjects using the G-band method, it is concluded that chromosome instabilities that could give rise to an increased frequency of persisting, exchange-type aberrations were not commonly generated by radiation exposure.
Kodama
Y
Y
Department of Genetics, Radiation Effects Research Foundation, 5-2 Hijiyama Park, Minami-ku, Hiroshima 732-0815, Japan. ykodama@rerf.or.jp
Ohtaki
K
K
Nakano
M
M
Hamasaki
K
K
Awa
A A
AA
Lagarde
F
F
Nakamura
N
N
D001943:Breast Neoplasms / Q000532:radiotherapy; D002478:Cells, Cultured; D043171:Chromosomal Instability; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D005188:False Negative Reactions; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007564:Japan; D008875:Middle Aged; D009689:Nuclear Warfare; D011336:Probability; D011878:Radiotherapy / Q000009:adverse effects; D013601:T-Lymphocytes / Q000528:radiation effects* / Q000648:ultrastructure