Sensitive detection of LOH events in a human cell line after C-ion beam exposure

Abstract

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.