ALPHA-PARTICLE MUTAGENESIS OF HUMAN LYMPHOBLASTOID CELL-LINES

Despite being derived from the same donor, the human lymphoblastoid ce ll lines WTK1 and TK6 have markedly different responses to low LET rad iation. We originally observed that WTK1 was more resistant to the cyt otoxic effects of X-irradiation, but significantly more sensitive to m utation induction at both the TK and HPRT loci. In an effort to better understand these properties, we have examined the effects of alpha-pa rticles on these cells. Relative to TK6, WTK1 has enhanced survival an d mutation after both X-ray and alpha-particle exposure. While the HPR T locus was significantly more mutable in WTK1 as a function of alpha- particle versus X-ray dose, the TK locus was only slightly more sensit ive to alpha-particle mutagenesis. In addition, the slowly growing TK mutants that constitute the majority of X-ray-induced TK mutants of TK 6 were recovered in lower proportions following alpha-particle exposur es. This is consistent with the further finding that in both cell line s, loss of heterozygosity occurred in a smaller fraction of ct-induced TK mutants than X-ray-induced mutants. These results are consistent w ith our previous model suggesting that WTK1 has an error-prone repair pathway that is either missing or deficient in TK6, and further sugges t that this pathway may be involved in the processing of alpha-particl e-induced damage.