The effect of DN (dominant-negative) Ku70 and reoxygenation on hypoxia cell-kill: Evidence of hypoxia-induced potentially lethal damage Journal Article
| Authors: | Urano, M.; Li, G. C.; He, F.; Minami, A.; Burgman, P.; Ling, C. C. |
| Article Title: | The effect of DN (dominant-negative) Ku70 and reoxygenation on hypoxia cell-kill: Evidence of hypoxia-induced potentially lethal damage |
| Abstract: | 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 096 h hypoxia. To reoxygenate medium were replaced fresh following 48 or 72 h in hypoxia and cells were incubated in aerobic environment for 224 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. © 2012 Informa UK, Ltd. |
| Keywords: | controlled study; unclassified drug; human cell; dna-binding proteins; colorectal cancer; cell proliferation; dna damage; cell survival; dna repair; apoptosis; oxygen; cancer cell culture; cancer therapy; hypoxia; cell damage; neoplasms, experimental; cell hypoxia; up-regulation; ku antigen; oxygen consumption; cell strain ht29; ht29 cells; cell killing; lethality; adenoviridae; reoxygenation; antigens, nuclear; potentially lethal damage; dnku70; dominant negative ku70 protein; cell strain hct8 |
| Journal Title: | International Journal of Radiation Biology |
| Volume: | 88 |
| Issue: | 7 |
| ISSN: | 0955-3002 |
| Publisher: | Taylor & Francis Group Ltd. |
| Date Published: | 2012-07-01 |
| Start Page: | 515 |
| End Page: | 522 |
| Language: | English |
| DOI: | 10.3109/09553002.2012.690548 |
| PROVIDER: | scopus |
| PUBMED: | 22617044 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 August 2012" - "CODEN: IJRBA" - "Source: Scopus" |
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