the time interval between the doses. Regeneration is a mechanism of
response to depopulation of a cell cohort due to radiation damage, and
depends on the types of tissue and their proliferating capacity. Protracting
a fractionated dose should be beneficial to normal tissues and somewhat
harmful to regenerating tumor cells. Reoxygenation discussed earlier is an
effect that makes the hypoxic cells more radiosensitive in the presence of
oxygen in fractionated radiotherapy.
Sublethal damage repair depends very much on the dose rate and in
which stage of the cell cycles the cells are. At lower doses, more SLD can
be repaired, and at higher doses, the chances of SLD repair diminish. The
dose-rate effect varies with the types of tissue and species. For example, the
testis of male rats is most radiosensitive, whereas the small intestine seems
to be less affected by radiation. Also, SLD repair depends on the LET of
radiations. The repair is significant with x-rays and g-rays and almost nonex-
istent for neutrons and a-particles. SLD repair is very important in radia-
tion therapy as it provides maximum survival of normal cells, while killing
tumor cells.
Potentially lethal damage after a single dose of radiation can potentially
kill the cell but it can be repaired (PLDR) under specific physicochemical
conditions. For example, the survival of the HeLa cells increased after
irradiation, when the cells were treated with excess thymidine or hydro-
xyurea for a period of 4 hr. However, opposite results were obtained by
other investigators. The importance of PLDR in radiotherapy is a matter of
debate.
PLDR and SLDR are found with low-LET radiations (e.g.,g-rays and x-
rays giving cell survival curves with a broad shoulder), while they are absent
for high-LET radiations (neutrons and a-particles).
Stochastic and Deterministic Effects
Two categories of radiation effects on biological systems are encountered:
stochastic and deterministic. Stochastic effects are the biological effects that
occur randomly, the probability of which increases with increasing dose
without a threshold. Radiation-induced hereditary effects and cancer inci-
dences are examples of stochastic effects. The assumption of no threshold
is made on the belief that radiation damage to a few cells or a single cell
could theoretically induce the genetic disorder or cancer, and the severity
of the disease will be the same, if it ever occurs. It should be noted that the
basic principle of ALARA (as low as reasonably achievable) in Nuclear
Regulatory Commission (NRC) regulations is based on the assumption of
risks linearly proportional to the dose without a threshold. Much debate is
currently going on regarding the assumption of the linear-no-threshold
(LNT) theory (discussed below).
246 15. Radiation Biology