PARENT SESSION
1:30 PM to 3:30 PM
Wednesday, April 24, 2002
Poster Session 30 Bystander Effects
Room: Nevada Exhibition Center

(P35-348) Radiation-induced chromosomal instability in normal human fibroblasts.

Dugan, Lawrence^*,1, Bedford, Joel¹, ¹ Department of Radiological Health Sciences, Fort Collins, CO

ABSTRACT-
Transmissible Genomic Instability (TGI) appears to be required for tumorigenesis. We have studied the frequency of induction of chromosomal instability using whole chromosome painting to measure the delayed appearance of transmissible aberrations in clones of AG 1521A normal, human fibroblasts surviving either high (⁵⁶Fe nuclei) or low (¹³⁷Cs -rays) LET radiation exposure. The cells were irradiated in G0 to attempt to simulate the non-cycling or slowly cycling state of many cells in tissues in vivo. A dose yielding ~10-20% survival and approximately 1 symmetrical exchange/cell was used. Clones were then isolated and studied 20-30 generations after irradiation. Whole chromosome painting probes for chromosomes 1, 2, 4 and X were hybridized to mitotic spreads by Fluorescence in situ Hybridization (FISH). The clones were then analyzed for karyotypic heterogeneity. Clones exhibiting 3 or more karyotypically different subpopulations were classified as unstable. Some 30-35% of clones were unstable after 125cGy of 1GeV/m ⁵⁶Fe nuclei or 500cGy of ¹³⁷Cs -rays. Next we set out to determine whether a dose dependent increase exists for ⁵⁶Fe nuclei irradiation of this cell line. G0 cells were irradiated at 0, 8.4, 16.7, 62.5 and 125cGy. Analysis was also done by FISH. Thus far, we have not seen a significant difference in the fraction of unstable clones for 62.5 vs. 125cGy ⁵⁶Fe nuclei. Supported by NIH grants T32 and CA09236 from NCI and RO1-CA73926 from NCI and NASA.

KEYWORDS: Transmissible genomic instability, Fluorescence in situ hybridization, radiation-induced chromosomal instability