Gamma-ray mutagenesis studies in a new human-hamster hybrid, A(L)CD59(+/-), which has two human chromosomes 11 but is hemizygous for the CD59 gene

We have developed a human-CHO hybrid cell Line, named A(L)CD59(+/-), which has two copies of human chromosome 11 but is hemizygous for the CD59 gene a nd the CD59 cell surface antigen that it encodes. Our previous studies used the A(L) and A(L)C hybrids that respectively contain one or two sets of CH O chromosomes plus a single copy of human chromosome 11. The CD59 gene at 1 1p13.5 and the CD59 antigen encoded by it are the principal markers used in our mutagenesis studies. The hybrid A(L)CD59(+/-) contains two copies of h uman chromosome II, only one of which carries the CD59 gene. The incidence of CD59- mutants (formerly called S1-) induced by Cs-137 gamma rays is abou t fivefold greater in A(L)CD59(+/-) cells than in A, cells, Evidence is pre sented that this increase in mutant yield is due to the increased induction of certain classes of large chromosomal mutations that are lethal to A, ce lls but are tolerated in the A(L)CD59(+/-) hybrid. In addition, significant ly more of the CD59 mutants induced by Cs-137 gamma rays in A(L)CD59(+/-) c ells display chromosomal instability than in A, cells. On the other hand, t he yield of gamma -ray-induced CD59 mutants in A(L)CD59(+/-) cells is half that of the A(L)C hybrid, which also tolerates very large mutations but has only one copy of human chromosome 11, We interpret the difference in mutab ility as evidence that repair processes involving the homologous chromosome s 11 play a role in determining mutant yields, The A(L)CD59(+/-) hybrid pro vides a useful new tool for quantifying mutagenesis and shedding light on m echanisms of genetic instability and mutagenesis. (C) 2001 by Radiation Res earch Society.