The majority of the radiation effect in photon therapy is caused by free radicals. Both single-stranded and double-stranded DNA damage can be repaired by cells. Double-stranded DNA breaks, on the other hand, are far more challenging to fix and can cause severe chromosomal abnormalities and genetic deletions. The likelihood that cells will die increases when double-stranded breaks are targeted. Cancer cells tend to be less differentiated and more stem cell-like; they procreate more frequently than the majority of healthy differentiated cells and have a reduced capacity to repair damage that is not life-threatening.
Damage to the single-strand DNA accumulates in cancer cells, leading them to die or divide more slowly. This damage is then transmitted through cell division. The oxygen depletion of solid tumor cells is one of the main drawbacks of photon Radiotherapy. Solid tumors may overrun their blood supply, resulting in hypoxia, a low oxygen condition. The formation of DNA-damaging free radicals by oxygen makes it a potent radiosensitizer, boosting the potency of a given dosage of radiation. Hypoxic conditions may make tumor cells up to two or three times more resistant to radiation damage than conditions with normal oxygen levels.
The use of high pressure oxygen tanks, hyperthermia therapy (heat therapy that dilates blood vessels to the tumor site), blood substitutes that carry increased oxygen, hypoxic cell radiosensitizer drugs like misonidazole and metronidazole, and hypoxic cytotoxins (tissue poisons), such as tirapazamine, have all been studied as ways to overcome hypoxia.
