Cellular and molecular studies of mutation induction by low energy heavy ions

Cellular and molecular studies of mutation induction by low energy heavy ions 1 first-author 1 2 3 Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York 10032; Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York 10032; The Genetics Group, Los Alamos National Laboratory, Los Alamos, NM 87545; The Genetics Group, Los Alamos National Laboratory, Los Alamos, NM 87545; Department of Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523 Department of Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523 Mutation induction by low energy heavy ions was scored at the hypoxanthine guanine phosphoribosyl transferase (HGPRT) locus using both normal human fibroblasts and the human-hamster hybrid A L cells. In addition, the mutation yield at a non-essential chromosome was also examined by using the S1 marker gene locating on human chromosome 11 in A L cells. Mutagenicity induced by low energy heavy ions was dose and LET dependent. The induced mutant fractions at the S1 locus were consistently higher than those for HGPRT. Using a mutation system that can detect multilocus changes, it can be shown by either Southern blotting or multiplex PCR techniques that radiation can induce chromosomal deletions in the millions of basepairs. Mutation Molecular spectrum Southern blot PCR Multilocus deletions References Hall E J , Hei T K . Radiat Protect Dos , 1985 ; 13 : 149 Radiat Protect Dos Hei T K , Chen D J , Brenner D J et al . Carcinogenesis , 1988 ; 9 : 1233 Carcinogenesis Geard C R . Radiation Res , 1985 ; 104S : 112 Radiation Res Yang T C , Craise L M , Mei M T et al . Radiat Res , 1985 ; 104 : S177 Radiat Res Hei T K , Komatsu K , Hall E J et al . Carcinogenesis , 1988 ; 9 : 747 Carcinogenesis Goodhead D T . Int J Radiat Biol , 1989 ; 56 : 558 Int J Radiat Biol Tsuboi K , Yang T C , Chen D . Radiat Res , 1992 ; 129 : 171 Radiat Res Kronenberg A , Little J B . Mutat Res , 1989 ; 211 : 215 Mutat Res Hall E J , Hei T K . Environ Helth Persp , 1990 ; 88 : 149 Environ Helth Persp Evans H H . Advances in Mut Res , 1991 ; 3 : 28 Advances in Mut Res Thacker J . Mutation Res , 1986 ; 49 : 1011 Mutation Res Hei T K , Zhu L X , Vannais D et al . Molecular analysis of mutagenesis by high LET radiation . Advances in Space Res. ( in press ). Molecular analysis of mutagenesis by high LET radiation Hei T K , Hall E J , Waldren C A . Radiat Res , 1988 ; 115 : 281 Radiat Res Hsie A W , Xu W , Yu Y et al . Terato Carcino Mut , 1990 ; 10 : 115 Terato Carcino Mut Evans H H , Mencl J , Hui T E et al . Radiat Res , 1993 ; 136 : 57 Radiat Res Puck T T , Wuchier P , Jones C et al . Proc Natl Acad Sci , 1971 ; 68 : 3102 Proc Natl Acad Sci Waldren C A , Jones C C , Puck T T . Proc Natl Acad Sci , 1979 ; 76 : 1358 Proc Natl Acad Sci Noyes E . Tissue Culture Association Manual , 1979 ; 5 : 1173 Tissue Culture Association Manual Waldren C A , Correall L , Sognier M A et al . Proc Natl Acad Sci , 1986 ; 83 : 4839 Proc Natl Acad Sci Southern E M . J Mol Biol , 1975 ; 98 : 503 J Mol Biol Mullis K B , Faloona F A . Methods in Enzymology , 1987 ; 155 : 335 Methods in Enzymology Hei T K , Zhu L X , Waldren C A . Molecular mechanisms of mutagenesis by radiation of different qualities . NATO ASI series H ( in press ) Molecular mechanisms of mutagenesis by radiation of different qualities Evans H H , Mencl J , Horng M F . Proc Natl Acad Sci , 1986 ; 83 : 4379 Proc Natl Acad Sci Liber H L , Yandell D W , Little J B . Mutation Res , 1989 ; 216 : 9 Mutation Res Jostes R F , Morgan T L , Gies R A et al . J Cell Biochem , 1990 ; S14A : 55 J Cell Biochem Morgan T , Fleck E W , Poston K A et al . Mutation Res , 1990 ; 232 : 171 Mutation Res This work was supported by the National Cancer Institute grants CA-49062, CA-56392, and by the National Institute of Environmental Health Sciences grant ES 05801 of the U.S. National Institute of Health. 1997-01-20 1997-05-01 2021-02-05 1997 Nuclear Science and Techniques 2 08