Sr. Wilt et al., USE OF FLUORESCENCE IN-SITU HYBRIDIZATION (FISH) TO STUDY CHROMOSOMALDAMAGE-INDUCED BY RADIATION AND BROMODEOXYURIDINE IN HUMAN COLON-CANCER CELLS, International journal of radiation oncology, biology, physics, 30(4), 1994, pp. 861-866
Citations number
20
Categorie Soggetti
Oncology,"Radiology,Nuclear Medicine & Medical Imaging
Purpose: Although the thymidine analog radiation sensitizer bromodeoxy
uridine (BrdUrd) increases radiation-induced chromosomal aberrations,
it is not known whether these aberrations are uniformly distributed am
ong chromosomes. Using fluorescence in situ hybridization, we carried
out a study to test the hypothesis that BrdUrd-induced radiosensitizat
ion may be mediated by nonuniform chromosomal damage. Methods and Mate
rials: Log phase HT29 human colon cancer cells were exposed to 10 mu M
BrdUrd (or media alone) for one cell cycle, and the G1 cells were sep
arated by centrifugal elutriation. Half of the control and BrdUrd samp
les were irradiated with 8 Gy. Cells were then incubated for 24-28 h,
and metaphase spreads were prepared. Fluorescence in situ hybridizatio
n was performed using paint probes for chromosomes 1 and 4. Results: W
e found that radiation induced 0.20 aberrations per chromosome in chro
mosome 4. Based on the ratio of the relative lengths of chromosome 1-4
(1.34), it was predicted that chromosome 1 would have approximate to
0.26 aberrations per chromosome. However, me 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 f
actor of 1.4) and chromosome 4 (by a factor of 1.9) compared to radiat
ion alone (p < 0.001 for both chromosome 1 and 4). Conclusion: This st
udy demonstrates that individual chromosomes in human colon cancer cel
ls show significantly different rates of aberration after irradiation.
Furthermore, the BrdUrd-mediated increase in radiation-induced chromo
somal aberrations may not be uniform among chromosomes.