these products concentrate more in normal cells and less in tumor cells. As
a result, normal cells are protected better than tumor cells if these agents
are administered immediately before the radiation dose is given. WR-2721,
also called amifostine, is an aminothial and protects bone marrow. Its most
common toxic effects are hypotension and somnalence. Radioprotectors
are most effective with low-LET radiations, because they cause minimal
damage.
Stage of Cell Cycle
Radiation damage mostly occurs during the period of mitosis, the M phase,
whereas least damage occurs during the DNA synthesis, the S phase. Thus,
the stage of the cell cycle determines the extent of radiation damage. Expo-
sure of cells to 100 to 1000 rad (100 to 1000 cGy) causes delay in the G 2
phase to M phase transition. An exposure of 1000 rad (1000 cGy) inhibits
the progression of the S phase cells by 30%, whereas the S phase to G 2
phase transition is not affected by such an exposure (Prasad, 1995).
Classification of Radiation Damage
Cell death is a measure of extreme radiation damage. Therefore, based on
the degree of lethality induced by radiation, radiation damage can be clas-
sified into three categories: (1) lethal damage, which causes irreversible
death; (2) sublethal damage (SLD), which normally repairs in hours, and
thus avoids cellular death, unless followed by another sublethal damage;
and (3) potentially lethal dose (PLD), which can potentially kill the cell but
can be modified to repair under specific physicochemical conditions. All
these damages are relevant in clinical radiation therapy as to the effective-
ness of treatment. Lethal damage is a definite end point in treatment,
whereas SLD and PLD have variable effects in radiation therapy.
Sublethal damage occurs in mammalian cells, when a radiation dose is
given in fractions at different time intervals rather than a single dose. There
are four mechanisms, the so-called four R’s that play a role in the SLD
repair (SLDR) mechanism: repair, redistribution, regeneration, and reoxy-
genation. Repair involves the healing of the radiation-induced damage in
the time interval between the two fractions of the dose. If the second dose
is applied too soon after the first application, the damage does not have
enough time to repair and the cell will die. In fractionated radiotherapy,
normal tissues are spared by SLD because of its repair mechanism. In the
redistribution process, the cells are desynchronized and sensitized to show
increased damage. Following irradiation, the radiosensitive cells will die,
and one would expect the proportion of radioresistant cells and hence the
surviving fraction to increase. In fact, however, the surviving cells become
sensitized and tend to die. This result depends on the fractionated dose and
Classification of Radiation Damage 245