Gamma-irradiation and doxorubicin treatment of normal human cells cause cell cycle arrest via different pathways.
Ionizing radiation and doxorubicin both produce oxidative damage and double-strand breaks in DNA. Double-strand breaks and oxidative damage are highly toxic and cause cell cycle arrest, provoking DNA repair and apoptosis in cancer cell lines. To investigate the response of normal human cells to agents causing oxidative damage, we monitored alterations in gene expression in F65 normal human fibroblasts. Treatment with g-irradiation and doxorubicin altered the expression of 23 and 68 known genes, respectively, with no genes in common. Both agents altered the expression of genes involved in cell cycle arrest, and arrested the treated cells in G2/M phase 12 h after treatment. 24 h after g-irradiation, the percentage of G1 cells increased, whereas after doxorubicin treatment the percentage of G2/M cells remained constant for 24 h. Our results suggest that F65 cells respond differently to g-irradiation- and doxorubicin-induced DNA damage, probably using entirely different biochemical pathways.
Lee
Seong Min
SM
School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea.
Youn
BuHyun
B
Kim
Cha Soon
CS
Kim
Chong Soon
CS
Kang
ChulHee
C
Kim
Joon
J
D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D015415:Biomarkers / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects* / Q000528:radiation effects*; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D004317:Doxorubicin / Q000633:toxicity*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects*; D005720:Gamma Rays; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects
D000903:Antibiotics, Antineoplastic; D015415:Biomarkers; D004317:Doxorubicin