Radiation for therapy is either x-rays produced by electrical machines called linear accelerators or gamma rays produced by the decay of radioactive isotopes such as cobalt. The radiation used in therapy is of very short wavelength. When an x-ray hits an atom or molecule in a cell it knocks off one of its electrons, forming unstable ions which can damage cells (hence the term ‘ionising radiation’).
As the x-ray beam passes through tissues it will randomly ionise cells in its path. Sometimes, it will hit the nucleus of a cell and sometimes the surrounding cytoplasm, or even the tissue outside the cell. The major target of radiation for cell killing is the DNA, but damage to other vital structures in the cell can also kill it by the indirect effect of the short-lived ions produced by the radiation. The important principle in killing a cell is to stop it dividing.
There is an old saying that a cancer cell doesn’t know it is dead until it tries to divide. This is fairly accurate and explains the delay between delivering the radiation and seeing a tumour shrink. Radiation can kill rapidly by turning on the program that leads to programmed cell death (apoptosis).
Often, however, it doesn’t kill the cell until the cell tries to divide, when the damage to the DNA will prevent this happening. In the meantime, the cell can remain functional. The cell may divide but produce sterile or abnormal offspring. The cell is most sensitive to radiation during the phase when the DNA strands are separating so that division into daughter cells can take place.
Not all the cells damaged by radiation die. Repair of the damage can occur, particularly after a low dose. Some cells are more resistant to radiation. Cells that are deprived of oxygen, such as those in the centre of a rapidly growing cancer, can be far more resistant than well oxygenated cells, for example. This gives us an insight into research directions in radiotherapy.
Attempts are being made to combine radiation with drugs that can sensitise cells to radiation, and sensitise oxygen-starved cells. Some chemotherapy drugs increase the efficacy of radiation either by sensitising cells to it, preventing any repair taking place, or just adding one way of killing to another.