Mutagenesis, Vol. 14, No. 2, 199-205,
March 1999
© 1999 UK Environmental Mutagen Society/Oxford University Press
Complex hprt deletion events are recovered after exposure of human lymphoblastoid cells to high-LET carbon and neon ion beams
1 Division of Radioisotope Technology, 2 Cellular Physiology Laboratory and 3 Cyclotron Laboratory, Institute of Physical and Chemical Research, Saitama 351-01, 4 Division of Biology, Toray Research Center Inc., Kanagawa 248, 5 Space and Particle Radiation Science Research Group, National Institute of Radiological Sciences, Chiba 263, 6 School of Medicine, Osaka University, Osaka 565 and 7 Faculty of Pharmacy, Nagasaki University, Nagasaki 852, Japan
Hypoxanthine phosphoribosyltransferase gene (hprt) mutations were induced in human TK-6 lymphoblastoid cells by irradiation at a linear energy transfer (LET) of 250 or 310 keV/µm for carbon and neon ions, respectively. At such a high level of LET, ions will lose most of their total energy and stop shortly after passing through the cell. The hprt mutations were analyzed by multiplex PCR, long-PCR and DNA sequencing of both genomic and cDNA. Over half of the C ion-induced hprt mutations (10 of 19) were point mutations, in contrast to 15% of the mutations induced by Ne ions (three of 20). The remaining 47 and 85% of the C and Ne ion-induced mutants, respectively, are deletion events. The latter events include three complex losses of multiple non-contiguous exon regions in both ion irradiation collections. We note that mutations involving the exon 6 region are frequent in the Ne ion collection: all three of the complex events retained the exon 6 region with flanking deletion of sequence and three other mutants involved deletion of this region. It may be concluded that these high-LET C and Ne ion irradiations produce different mutational spectra.
8 To whom correspondence should be addressed at: Division of Radioisotope Technology, Institute of Physical and Chemical Research, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan. Tel: +81 48 467 9566; Fax: +81 48 462 4636; Email: yatagai{at}postman.riken.go.jp