Sensitive detection of LOH events in a human cell line after C-ion beam exposure.
A molecular analysis of the loss of heterozygosity (LOH) events in human cells after low-dose heavy-ion exposure could contribute to the sensitive detection of the genetic influences caused by high-LET radiation. We exposed human lymphoblastoid TK6-20C cells to 10 cGy of an accelerated C-ion (22 keV/microm) beam, and observed a 3.1-fold increase in the mutation frequency (MF) at the heterozygous thymidine kinase (TK) locus over the background level. This increase was due to the induction of TK mutants exhibiting hemizygous-type LOH. Surprisingly, the frequency of type-2 hemizygous LOHs (interstitial deletions) was about 23-fold, induced over the background level, and the LOH extent patterns of this type 2 induced after the irradiation were clearly different from that of the spontaneous background.. Since hemizygous-type LOH mutants are considered to be the result of the end-joining repair of DNA double-strand breaks (DSB), C-ions may more efficiently induce DSBs than X-rays in this low-dose region. In addition, an enhanced misrepair of C-ion-induced DSBs might also account for the induction of radiation-specific hemizygous-type LOH.
Morimoto
Shigeko
S
Division of Radioisotope Technology, The Institute of Physical and Chemical Research (RIKEN), Saitama 351-0198, Japan.
Honma
Masamitsu
M
Yatagai
Fumio
F
D002244:Carbon; D002874:Chromosome Mapping; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D005787:Gene Frequency; D020450:Heavy Ions; D006579:Heterozygote; D006801:Humans; D019656:Loss of Heterozygosity; D008214:Lymphocytes / Q000528:radiation effects*; D009154:Mutation; D013937:Thymidine Kinase / Q000235:genetics; D014407:Tumor Cells, Cultured
D002244:Carbon; D004247:DNA; D013937:Thymidine Kinase