PMID- 7960988 OWN - NLM STAT- MEDLINE DCOM- 19941215 LR - 20190708 IS - 0360-3016 (Print) IS - 0360-3016 (Linking) VI - 30 IP - 4 DP - 1994 Nov 15 TI - Use of fluorescence in situ hybridization (FISH) to study chromosomal damage induced by radiation and bromodeoxyuridine in human colon cancer cells. PG - 861-6 AB - PURPOSE: Although the thymidine analog radiation sensitizer bromodeoxyuridine (BrdUrd) increases radiation-induced chromosomal aberrations, it is not known whether these aberrations are uniformly distributed among chromosomes. Using fluorescence in situ hybridization, we carried out a study to test the hypothesis that BrdUrd-induced radiosensitization may be mediated by nonuniform chromosomal damage. METHODS AND MATERIALS: Log phase HT29 human colon cancer cells were exposed to 10 microM BrdUrd (or media alone) for one cell cycle, and the G1 cells were separated by centrifugal elutriation. Half of the control and BrdUrd samples were irradiated with 8 Gy. Cells were then incubated for 24-28 h, and metaphase spreads were prepared. Fluorescence in situ hybridization was performed using paint probes for chromosomes 1 and 4. RESULTS: We found that radiation induced 0.20 aberrations per chromosome in chromosome 4. Based on the ratio of the relative lengths of chromosome 1-4 (1.34), it was predicted that chromosome 1 would have approximately 0.26 aberrations per chromosome. However, we observed 0.39 aberrations per chromosome 1, which was significantly greater than the predicted (p < 0.001 by chi-square). Incubation with BrdUrd prior to irradiation significantly increased the aberrations found in chromosome 1 (by a factor of 1.4) and chromosome 4 (by a factor of 1.9) compared to radiation alone (p < 0.001) for both chromosome 1 and 4). CONCLUSION: This study demonstrates that individual chromosomes in human colon cancer cells show significantly different rates of aberration after irradiation. Furthermore, the BrdUrd-mediated increase in radiation-induced chromosomal aberrations may not be uniform among chromosomes. FAU - Wilt, S R AU - Wilt SR AD - Department of Radiation Oncology, School of Medicine, University of Michigan Medical Center, Ann Arbor 48109-0582. FAU - Burgess, A C AU - Burgess AC FAU - Normolle, D P AU - Normolle DP FAU - Trent, J M AU - Trent JM FAU - Lawrence, T S AU - Lawrence TS LA - eng GR - CA 42761/CA/NCI NIH HHS/United States GR - CA 46592/CA/NCI NIH HHS/United States GR - CA 53440/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Int J Radiat Oncol Biol Phys JT - International journal of radiation oncology, biology, physics JID - 7603616 RN - 0 (Radiation-Sensitizing Agents) RN - G34N38R2N1 (Bromodeoxyuridine) SB - IM MH - Bromodeoxyuridine/*pharmacology MH - Cell Cycle/drug effects/physiology MH - *Chromosome Aberrations MH - Chromosomes, Human, Pair 1/*drug effects/*radiation effects MH - Chromosomes, Human, Pair 4/*drug effects/*radiation effects MH - Colonic Neoplasms/drug therapy/*genetics/*radiotherapy MH - G1 Phase/drug effects/physiology MH - Humans MH - *In Situ Hybridization, Fluorescence MH - Karyotyping MH - Radiation Injuries/etiology MH - Radiation Tolerance/*drug effects/*physiology MH - Radiation-Sensitizing Agents/*pharmacology MH - Tumor Cells, Cultured/drug effects/radiation effects EDAT- 1994/11/15 00:00 MHDA- 1994/11/15 00:01 CRDT- 1994/11/15 00:00 PHST- 1994/11/15 00:00 [pubmed] PHST- 1994/11/15 00:01 [medline] PHST- 1994/11/15 00:00 [entrez] AID - 0360-3016(94)90361-1 [pii] AID - 10.1016/0360-3016(94)90361-1 [doi] PST - ppublish SO - Int J Radiat Oncol Biol Phys. 1994 Nov 15;30(4):861-6. doi: 10.1016/0360-3016(94)90361-1.