of the blood vessels find themselves closer to the blood supply and so
reoxygenate.
Pyrimidines
Halogenated pyrimidines such as 5-chlorodeoxyuridine (ClUDR), 5-
bromodeoxyuridine (BUDR), and 5-iododeoxyuridine (IUDR) are useful
radiosensitizers. When cells are treated with these drugs for several days
before irradiation with x- or g-rays, cells become highly sensitive to radia-
tion. Potentiation of radiosensitivity is due to the fact that these drugs are
similar to the DNA precursor thymidine, and therefore are incorporated
into the DNA molecule, making them more susceptible to damage by radi-
ation. For optimal therapeutic gain in radiotherapy, patients should be
treated for a period of time extending over several cell cycles to maximize
drug incorporation into the cells.
Others
Radiosensitizers such as actinomycin D, puromycin, methotrexate, and 5-
fluorouracil have been successfully used in combination with radiation to
treat cancer. Whether these agents truly increase radiosensitivity or are
simply toxic to the cells is still not clear.
Investigators have been trying to explore radiosensitizing chemicals to
substitute for oxygen that requires the use of a high-pressure technique.
Metronidazole (Flagyl), having a structure with high electron affnity, is a
good radiosensitizer for hypoxic cells. Another useful radiosensitizer for
hypoxic cells is misonidazole, which also has high electron affnity. Mis-
onidazole is almost ten times more effective than metronidazole in sensi-
tizing hypoxic cells. However, clinical trials with this agent provided only
disappointing results. Another radiosensitizer of this kind is etanidazole,
which is less toxic than misonidazole, and has great potential in radio-
therapy. Most side effects of these products are related to neurotoxicity.
These compounds are described as “oxygen mimics.”
Radioprotectors
The most common radioprotectors—substances that protect cells from radi-
ation damage—include substances containing sulfhydryl groups (-SH), such
as cysteine and cysteamine. These agents protect normal cells from radia-
tion damage by combining with free radicals that are produced by radia-
tion and would be toxic to normal cells. However, these compounds cause
severe adverse reactions such as nausea and vomiting.
Less toxic compounds have been developed in which the -SH group is
protected by a phosphate group. The phosphate group is hydrolyzed in vivo
to release the -SH group for radioprotection. Two most effective com-
pounds of this category are WR-638 and WR-2721 developed at Walter
Reed Army Hospital, Washington, DC. Experimental evidence showed that
244 15. Radiation Biology