TY - JOUR
T1 - Alpha particle mutagenesis of human lymphoblastoid cell lines
AU - Amundson, S. A.
AU - Chen, D. J.
AU - Okinaka, R. T.
N1 - Funding Information:
This work was perform ed under the auspices of the US Departm ent of Energy under contract KP0400/005181 to th e Los Alam os National Laboratory. Additional support was provided by NIH grant CA5644 to D JC and a Los Alam os N ational Labo ratory Director’s Postdoctoral Fellowship (SAA). We would like to thank Rachel Palm er and Melissa H ankins for technical assistance.
PY - 1996
Y1 - 1996
N2 - Despite being derived from the same donor, the human lymphoblastoid cell lines WTK1 and TK6 have markedly different responses to low LET radiation. We originally observed that WTK1 was more resistant to the cytotoxic effects of X-irradiation, but significantly more sensitive to mutation induction at both the TK and HPRT loci. In an effort to better understand these properties, we have examined the effects of α-particles on these cells. Relative to TK6, WTK1 has enhanced survival and mutation after both X-ray and α-particle exposure. While the HPRT locus was significantly more mutable in WTK1 as a function of α-particle versus X-ray dose, the TK locus was only slightly more sensitive to a-particle mutagenesis. In addition, the slowly growing TK mutants that constitute the majority of X-ray-induced TK mutants of TK6 were recovered in lower proportions following α-particle exposures. This is consistent with the further finding that in both cell lines, loss of heterozygosity occurred in a smaller fraction of α-induced TK mutants than X-ray-induced mutants. These results are consistent with our previous model suggesting that WTK1 has an error-prone repair pathway that is either missing or deficient in TK6, and further suggest that this pathway may be involved in the processing of α-particle-induced damage.
AB - Despite being derived from the same donor, the human lymphoblastoid cell lines WTK1 and TK6 have markedly different responses to low LET radiation. We originally observed that WTK1 was more resistant to the cytotoxic effects of X-irradiation, but significantly more sensitive to mutation induction at both the TK and HPRT loci. In an effort to better understand these properties, we have examined the effects of α-particles on these cells. Relative to TK6, WTK1 has enhanced survival and mutation after both X-ray and α-particle exposure. While the HPRT locus was significantly more mutable in WTK1 as a function of α-particle versus X-ray dose, the TK locus was only slightly more sensitive to a-particle mutagenesis. In addition, the slowly growing TK mutants that constitute the majority of X-ray-induced TK mutants of TK6 were recovered in lower proportions following α-particle exposures. This is consistent with the further finding that in both cell lines, loss of heterozygosity occurred in a smaller fraction of α-induced TK mutants than X-ray-induced mutants. These results are consistent with our previous model suggesting that WTK1 has an error-prone repair pathway that is either missing or deficient in TK6, and further suggest that this pathway may be involved in the processing of α-particle-induced damage.
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U2 - 10.1080/095530096145210
DO - 10.1080/095530096145210
M3 - Article
C2 - 8794851
AN - SCOPUS:0029836905
SN - 0955-3002
VL - 70
SP - 219
EP - 226
JO - International Journal of Radiation Biology
JF - International Journal of Radiation Biology
IS - 2
ER -