title: 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.
abstract: Kraemer, S. M., Vannais, D. B., Kronenberg, A., Ueno, A. and Waldren, C. A. 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. Radiat. Res. 156, 10-19 (2001). 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 and 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 CHO chromosomes plus a single copy of human chromosome 11. The CD59 gene at 11p13.5 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 human chromosome 11, only one of which carries the CD59 gene. The incidence of CD59 (-) mutants (formerly called S1(-)) induced by (137)Cs gamma rays is about fivefold greater in A(L)CD59(+/-) cells than in A(L) cells. Evidence is presented that this increase in mutant yield is due to the increased induction of certain classes of large chromosomal mutations that are lethal to A(L) cells but are tolerated in the A(L)CD59(+/-) hybrid. In addition, significantly more of the CD59 (-) mutants induced by (137)Cs gamma rays in A(L)CD59(+/-) cells display chromosomal instability than in A(L) cells. On the other hand, the 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 mutability as evidence that repair processes involving the homologous chromosomes 11 play a role in determining mutant yields. The A(L)CD59(+/-) hybrid provides a useful new tool for quantifying mutagenesis and shedding light on mechanisms of genetic instability and mutagenesis.
authors: Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA. skraemer@lamar.colostate.edu
authors: S M
authors: SM
authors: Kraemer
authors: D B
authors: DB
authors: Vannais
authors: A
authors: A
authors: Kronenberg
authors: A
authors: A
authors: Ueno
authors: C A
authors: CA
authors: Waldren
mesh_terms: D000818:Animals; D018957:CD59 Antigens / Q000235:genetics*; D016466:CHO Cells; D002459:Cell Fusion; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D006224:Cricetinae; D004252:DNA Mutational Analysis; D004260:DNA Repair / Q000235:genetics / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000166:cytology; D005720:Gamma Rays; D018628:Gene Dosage; D005819:Genetic Markers; D006801:Humans; D006822:Hybrid Cells / Q000166:cytology / Q000528:radiation effects*; D017404:In Situ Hybridization, Fluorescence; D016296:Mutagenesis / Q000528:radiation effects*; D016133:Polymerase Chain Reaction
chemical_list: D018957:CD59 Antigens; D005819:Genetic Markers