Characterization of a potential radiation-sensitive fragile site

Journal Article · Wed Nov 01 04:00:00 EST 1995 · Environmental and Molecular Mutagenesis

OSTI ID:115130

Jordan, R; Oroskar, A A; Sedita, B A ^[1]

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1. Argonne National Laboratory, IL (United States); and others

We have been characterizing a Chinese hamster ovary cell line, CHO-K1 10T5, into which a gpt-containing retroviral shuttle vector has been stably integrated. This normally stable locus in CHO-K1 10T5 cells is very sensitive to deletion mutation following ionizing radiation exposure and shows an LET response with an RBE of 3 for {alpha} particles. Almost all of the gpt mutants are total gene deletions. The gpt gene has been localized to chromosome 5q15, within 100-1000 kb of a large region of interstitial telomere repeats. In addition, sequences showing homology to telomere repeat sequences have been identified at the integration site both 5` and 3` to the gpt gene locus. The integration site has been cloned and is presently being sequenced. Preliminary data suggest that there is a hotspot for breakage and/or recombination 5` of the integration site. We hypothesize that (1) the gpt vector has integrated into a region containing telomere repeat sequences, (2) this region of the genome is a radiation-sensitive fragile site, and (3) the radiation sensitivity of this site is due to the telomere sequences, which act by either serving as a site for further telomerase action and chromosome terminilization, or by providing repeat structures to facilitate radiation-induced recombination.

• Research Organization: Argonne National Laboratory (ANL), Argonne, IL
• DOE Contract Number: W-31109-ENG-38; FG02-88ER60661
• OSTI ID: 115130
• Report Number(s): CONF-9503160--; CNN: Grant CA 42596
• Journal Information: Environmental and Molecular Mutagenesis, Journal Name: Environmental and Molecular Mutagenesis Journal Issue: Suppl.25 Vol. 25; ISSN 0893-6692; ISSN EMMUEG
• Country of Publication: United States
• Language: English

Related Subjects

56 BIOLOGY AND MEDICINE
APPLIED STUDIES
BIOLOGICAL INDICATORS
CHO CELLS
GENES
GENETIC RADIATION EFFECTS