Radiation-Induced Apoptosis in Thymocytes: pH Sensitization

Ojeda, F. Patricio; Skardova, I.; Guarda, M.I.; Maldonado, Carmen; Folch, Hugo

doi:10.1515/znc-1996-5-624

Cited by 5 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although an acidic extracellular pH may enhance radiation-induced expression of p53 [83], several studies have shown that low pH ( ∼ 6.5) inhibits or at least delays radiation-induced apoptosis (Table 2) [84][85][86][87][88][89] (also see Fig. 3).…”

Section: Is Radiation-induced Apoptosis Modulated By Ph?mentioning

confidence: 94%

“…In one of the aforementioned studies, both an acute (30 min) and a chronic (3 month) exposure to pH 6.8 reduced apoptosis caused by radiation [88]. Radiation-induced apoptosis was enhanced significantly in thymocytes when pH was raised from 7 to 8 [84]. Experiments with murine mammary adenocarcinoma cells indicate a similar response [85].…”

Section: Is Radiation-induced Apoptosis Modulated By Ph?mentioning

confidence: 97%

See 1 more Smart Citation

Does the tumor microenvironment influence radiation-induced apoptosis?

et al. 2006

View full text Add to dashboard Cite

show abstract

Section: Is Radiation-induced Apoptosis Modulated By Ph?mentioning

confidence: 94%

Section: Is Radiation-induced Apoptosis Modulated By Ph?mentioning

confidence: 97%

Does the tumor microenvironment influence radiation-induced apoptosis?

et al. 2006

View full text Add to dashboard Cite

show abstract

“…The phase of the cell cycle also affects radiation responses, with cells in G2/M and G1 phases the most radiosensitive and those in the S phase more radioresistant [ 91 , 92 ]. Increased acidification decreases the effectiveness of radiation; cells cultured in acidic media are more resistant to radiation, with acidic pH e shown to reduce fixation of radiation-induced DNA damage, inhibit radiation-induced apoptosis, and delay G2/M-phase arrest allowing more time for treated cells to repair DNA damage, thus increasing radioresistance [ 7 , 93 , 94 , 95 , 96 , 97 , 98 , 99 ].…”

Section: Radiationmentioning

confidence: 99%

Carbonic Anhydrase IX (CAIX), Cancer, and Radiation Responsiveness

et al. 2018

View full text Add to dashboard Cite

Carbonic anhydrase IX has been under intensive investigation as a therapeutic target in cancer. Studies demonstrate that this enzyme has a key role in pH regulation in cancer cells, allowing these cells to adapt to the adverse conditions of the tumour microenviroment. Novel CAIX inhibitors have shown efficacy in both in vitro and in vivo pre-clinical cancer models, adversely affecting cell viability, tumour formation, migration, invasion, and metastatic growth when used alone. In co-treatments, CAIX inhibitors may enhance the effects of anti-angiogenic drugs or chemotherapy agents. Research suggests that these inhibitors may also increase the response of tumours to radiotherapy. Although many of the anti-tumour effects of CAIX inhibition may be dependent on its role in pH regulation, recent work has shown that CAIX interacts with several of the signalling pathways involved in the cellular response to radiation, suggesting that pH-independent mechanisms may also be an important basis of its role in tumour progression. Here, we discuss these pH-independent interactions in the context of the ability of CAIX to modulate the responsiveness of cancer to radiation.

show abstract

“…Indeed, there is evidence that pH may radiosensitize to apoptosis. 51 Previous studies have indicated that low pH can delay radiation-induced apoptosis after low doses (12 Gy and below) due to temporary pH-related cell cycle arrest. 42,43 Other studies using higher doses (20 Gy) 42 demonstrated an inhibition due to cycle delay-independent mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Radiation-induced apoptosis is modulated by the post-irradiation tumor microenvironment

Hunter

Hendrikse²,

Renan³

2009

Cancer Biology & Therapy

View full text Add to dashboard Cite

The sensitivity of cells to radiation-induced apoptosis is considered to be low in solid tumors. This is thought to arise largely from inherent resistance caused by apoptotic pathway mutations. However, other factors may contribute to apoptotic resistance. Poor vasculature and abnormal tumor metabolism lead to a tumor microenvironment characterized by conditions of hypoxia, low glucose and extracellular acidosis. Hypoxia during irradiation is well known to cause resistance and is a barrier to successful treatment. We hypothesized that post-irradiation microenvironmental conditions can modulate radiation-induced apoptosis and that this may in part contribute to therapeutic resistance. In order to test this, radiation-induced apoptosis was assessed in U937 cells in suspension and in a novel multicellular agarose-diffusion-system. Post-irradiation hypoxia failed to modify the extent of apoptosis in suspension cells, suggesting that post-irradiation hypoxia may be of little consequence to apoptosis induction in this model. In contrast, low glucose post-irradiation significantly inhibited radiation-induced apoptosis. While short (five hours) exposure to acidosis also appeared to inhibit radiation-induced apoptosis, the lack of modulation after extended (20 hours) exposure suggests that acidosis may only delay apoptosis. In the more complex agarose diffusion-limitation model, radiation-induced apoptotic sensitivity was found to be reduced in cells distant from the diffusion edge representing poorly perfused tumor cells in vivo. Overall, the results suggest that the post-irradiation tumor microenvironment may affect radiation-induced apoptosis and thus may influence therapeutic response. Therefore, the post-irradiation tumor microenvironment may be a target for therapeutic intervention.

show abstract

Radiation-Induced Apoptosis in Thymocytes: pH Sensitization

Cited by 5 publications

References 0 publications

Does the tumor microenvironment influence radiation-induced apoptosis?

Does the tumor microenvironment influence radiation-induced apoptosis?

Carbonic Anhydrase IX (CAIX), Cancer, and Radiation Responsiveness

Radiation-induced apoptosis is modulated by the post-irradiation tumor microenvironment

Contact Info

Product

Resources

About