Abstract:
:We studied the role of cysteine as an intracellular radiation protector under conditions in which both oxygen and thiols were monitored at 37 degrees C. In HCT-116 human colon cancer cells, the intracellular cysteine content affects the radiation survival dramatically at intermediate oxygen levels, but not at zero or high oxygen levels. Using a spin-through-oil method with a dual radioactive label detection system, we measured intracellular cysteine and glutathione (GSH) levels for cells in suspension culture. A comparison of the cysteine levels of monolayer cells lysed in situ and of trypsinized monolayer cells in suspension (Horan et al., Cytometry 29, 76-82, 1997) revealed that, upon trypsinization from monolayer culture and transfer to a spinner apparatus at 37 degrees C, HCT-116 cells lose most of their intracellular cysteine. Over the 60-min time course of control experiments, these cells do not recover intracellular cysteine despite the availability of cystine (the disulfide of cysteine) in the medium. When cells in spinner culture are provided with exogenous cysteine, they initially concentrate it to 10-fold the extracellular concentration, with the concentration factor decreasing to about 5-fold over the course of an hour. The intracellular GSH concentration changes little throughout this period, regardless of the changes in cysteine levels. The same apparatus was used to assess the survival of HCT-116 cells irradiated at 37 degrees C under conditions of constant pO(2) monitoring. For cells without added cysteine, the oxygen concentration for half-maximal radiation sensitivity was about 7.5 mmHg (intermediate hypoxia), more than twice the commonly accepted value (3 mmHg). At 7.5 mmHg, cells with added cysteine (intracellular concentration 3.5 mM) were almost as radioresistant as severely hypoxic cells (approximately 0.005% oxygen). Cells in parallel experiments in which the cells were grown in monolayers on glass Petri dishes had intermediate cysteine values and also intermediate radiosensitivity. We conclude that the radiation response of cells at intermediate oxygen levels is controlled predominantly by intracellular cysteine levels and that the cysteine levels commonly found in tumors may increase the K(m) for radiosensitivity to values much higher than suggested previously.
journal_name
Radiat Resjournal_title
Radiation researchauthors
Horan AD,Koch CJdoi
10.1667/0033-7587(2001)156[0388:tkmfro]2.0.co;2subject
Has Abstractpub_date
2001-10-01 00:00:00pages
388-98issue
4eissn
0033-7587issn
1938-5404journal_volume
156pub_type
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journal_title:Radiation research
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journal_title:Radiation research
pub_type: 杂志文章
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更新日期:1994-10-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
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更新日期:1986-04-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1988-06-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章,评审
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更新日期:2010-12-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1986-10-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1984-09-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1994-11-01 00:00:00
abstract::Radiation-induced acute myeloid leukemia (rAML) in C3H mice is commonly developed through inactivation of PU.1 transcription factor encoded in Sfpi1 on chromosome 2. PU.1 inactivation involves two steps: hemizygous deletion of the Sfpi1 gene (DSG) and point mutation of the allele Sfpi1 gene (PMASG). In this study, we ...
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journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1991-10-01 00:00:00
abstract::To accurately quantify the number of single-strand breaks (SSBs) induced in plasmid DNA molecules after irradiation, a new type of assay methodology has been explored. The new method is based on the TUNEL (terminal deoxynucleotide transferase dUTP nick end-labeling) assay that was adopted for use under ELISA (enzyme-l...
journal_title:Radiation research
pub_type: 杂志文章
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更新日期:2009-11-01 00:00:00
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pub_type: 杂志文章
doi:10.1667/0033-7587(2001)155[0785:odfrti]2.0.co;2
更新日期:2001-06-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/RR2927.1
更新日期:2013-02-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/rr3319
更新日期:2005-03-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
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doi:
更新日期:1998-10-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
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更新日期:2002-05-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1991-10-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1994-04-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1996-07-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1987-08-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1992-03-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:10.1667/0033-7587(2000)153[0752:ctitab]2.0.co;2
更新日期:2000-06-01 00:00:00