The effect of DN (dominant-negative) Ku70 and reoxygenation on hypoxia cell-kill: Evidence of hypoxia-induced potentially lethal damage

Purpose: To study the effect of DN (dominant-negative) Ku70 and reoxygenation on the hypoxia-induced cell-kill. Materials and methods: Cell lines were human colorectal carcinoma HCT8 and HT29 cells and their respective derivatives, v-HCT8 and v-HT29 infected with DNKu70-containing adenovirus. Cells...

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Published in:International journal of radiation biology 2012-07, Vol.88 (7), p.515-522
Main Authors: Urano, Muneyasu, Li, Gloria C., He, Fuqiu, Minami, Akiko, Burgman, Paul, Ling, C. Clifton
Format: Article
Language:English
Subjects:
Antigens, Nuclear - genetics
Antigens, Nuclear - metabolism
Apoptosis
Cell Hypoxia
Cell Proliferation
Cell Survival
DNA Damage
DNA Repair
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
DNKu70
HT29 Cells
Humans
hypoxia
Ku Autoantigen
Neoplasms, Experimental - pathology
Neoplasms, Experimental - physiopathology
Oxygen - metabolism
Oxygen Consumption
Potentially lethal damage
reoxygenation
Space life sciences
Up-Regulation
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Summary:Purpose: To study the effect of DN (dominant-negative) Ku70 and reoxygenation on the hypoxia-induced cell-kill. Materials and methods: Cell lines were human colorectal carcinoma HCT8 and HT29 cells and their respective derivatives, v-HCT8 and v-HT29 infected with DNKu70-containing adenovirus. Cells were plated in glass tubes and made hypoxic by flushing N2 gas containing 0, 0.1 or 0.5% O2. Cell survival was determined by colony formation assay immediately after 0-96 h hypoxia. To reoxygenate medium were replaced fresh following 48 or 72 h in hypoxia and cells were incubated in aerobic environment for 2-24 h before survival assay. Results: When incubated in hypoxia, cells lost reproductive capability ∼ exponentially as a function of time in hypoxia, and depending on the O2 concentration. DNKu70 rendered cells more prone to hypoxia-induced cell-kill. Following reoxygenation cell survival increased rapidly but without detectable cell proliferation during first 24 hours. This evinced hypoxia-induced potentially lethal damage (PLD) that was repairable upon reoxygenation. DNKu70 did not significantly inhibit this repair. Conclusion: Hypoxia-induced cell lethality was facilitated by DNKu70, but substantially repaired upon reoxygenation. This may have negative impact on the effect of reoxygenation in cancer therapy.
ISSN:0955-3002
1362-3095
DOI:10.3109/09553002.2012.690548