“…Pertinent to this question is a report that an acidic environment renders cells resistant to radiationinduced clonogenic cell death. 12 An acidic environment lowers the intracellular pH, although there are a number of cellular mechanisms which prevent drastic changes in the intracellular pH. 40 Mechanisms by which acidic extracellular environment causes apoptosis and alters the radiation response of cells are being investigated in our laboratory.…”
Section: Discussionmentioning
confidence: 99%
“…9 ± 12 On the other hand, an acidic environment has been reported to increase radioresistance of tumor cells. 12 We have found that an acidic environment suppresses the exit of cells from radiationinduced G2/M arrest, thereby suppressing radiation-induced apoptosis in SCK mouse tumor cells 13 and also in HL-60 human leukemia cells. 14 It is well established that the tumor suppressor gene p53 is intimately involved in cell cycle progression and apoptosis in irradiated cells.…”
We investigated the effect of an acidic environment on the radiation-induced G2/M arrest and apoptosis using RKO×C human colorectal cancer cells expressing wild-type p53 and RC10×1 cells, a subline of RKO×C cells deficient in p53 as well as p53 +/+ MEFs and p53 7/7
“…Pertinent to this question is a report that an acidic environment renders cells resistant to radiationinduced clonogenic cell death. 12 An acidic environment lowers the intracellular pH, although there are a number of cellular mechanisms which prevent drastic changes in the intracellular pH. 40 Mechanisms by which acidic extracellular environment causes apoptosis and alters the radiation response of cells are being investigated in our laboratory.…”
Section: Discussionmentioning
confidence: 99%
“…9 ± 12 On the other hand, an acidic environment has been reported to increase radioresistance of tumor cells. 12 We have found that an acidic environment suppresses the exit of cells from radiationinduced G2/M arrest, thereby suppressing radiation-induced apoptosis in SCK mouse tumor cells 13 and also in HL-60 human leukemia cells. 14 It is well established that the tumor suppressor gene p53 is intimately involved in cell cycle progression and apoptosis in irradiated cells.…”
We investigated the effect of an acidic environment on the radiation-induced G2/M arrest and apoptosis using RKO×C human colorectal cancer cells expressing wild-type p53 and RC10×1 cells, a subline of RKO×C cells deficient in p53 as well as p53 +/+ MEFs and p53 7/7
“…The interaction between reduced extracellular pH and radiation has also been investigated [9,11,21,28,29]. The interest in the effects of an acidic milieu is based on the finding that tumors frequently have a rather low interstitial pH; values below 6.0 may be found in certain tumors, whereas typical values in healthy tissues are between 7.0 and 7.2 (for review, see [16,34]).…”
In contrast to the almost generally accepted hypothesis that intracellular pH is decisive for the heat sensitivity, the human melanoma cells studied here became sensitive after a few days of incubation under acidic conditions without changes in the intracellular pH. Other factors seem to be influencing the cellular response to radiation and/or heat under chronically low pH.
“…It had clinical consequences, too, since anticancer treatments were often designed to take advantage of a low pH, (for a review, see WikeHooley et al, 1984). It was argued, for instance, that anticancer drugs would be more effective if they contained ionising groups that would cause them to be trapped in acidic environments (Wike-Hooley et al, 1984), or that radioresistant hypoxic cells would have a particularly low pHi and might therefore be especially sensitive to treatments such as hyperthermia which are known to act preferentially on isolated cells in acidic media (Freeman et al, 1981). There were also numerous attempts to lower pHi still further by administration of glucose, and thereby enhance the action of various pH-sensitive therapies (Ross, 1961, reviewed by Wike-Hooley et al, 1984).…”
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