Suppressor genes exist in normal cells to control the cell growth and
protect the genome against carcinogenic agents. After radiation damage,
suppressor genes stop cell division and repair the damaged gene. Examples
of suppressor genes include the p53 gene found in breast cancer, small cell
lung cancer, and bladder cancer; the DCC gene in colon cancer; and the
p105 Rb gene in retinoblastoma. Radiation can inactivate these suppressor
genes and thus cause cell proliferation leading to malignancy.
Epidemiologic Evidence of Carcinogenesis
The latent period of malignancies varies with the type of malignancy
and the absorbed dose. Leukemia has an average latent period of about
5 to 10 years, whereas solid tumors in the head, neck, pharynx, and
thyroid have a minimum latent period of 10 years with an average of 20 to
30 years.
Malignancies have been observed in individuals who are exposed to radi-
ation from medical treatment, radiation-related occupation (e.g., industrial
exposure), and acts of war. Infants and children are more radiosensitive
than adults, and the risk of cancer from radiation exposure in the former is
greater than that in the latter, almost by a factor of 2.
In the early 1900s, radium-dial painters used to lick the brush bristle
soaked with radium-containing paint to make a fine point for painting clock
and watch dials. During the procedure, they ingested radium, which, as a
chemical analog of calcium, localized in bone, causing bone tumors. In some
cases, the quantity of radium ingested was large, and acute effects includ-
ing death were observed.
Before the 1930s, the enlarged thymus gland of infants with acute respi-
ratory distress syndromes was commonly treated with therapeutic doses of
x-rays to reduce the enlargement. During irradiation, however, the thyroid
glands also received a massive radiation dose. A statistically significant
number of these infants developed thyroid cancer later in life (about 10
years later).
Radiologists who used x-rays in their profession were found to have a
higher incidence of leukemia than other medical professionals. Dentists had
higher incidence of finger lesions due to exposure to dental x-rays. These
incidences occurred mostly before the 1950s, largely because of the lack of
knowledge of radiation effects. Now, through better radiation protection
practice, these incidences have been curtailed drastically.
From 1935 to 1944, approximately 15,000 patients with ankylosing
spondilytis were irradiated with 100 to 2000 R over spine and pelvis. A 2-
year follow-up showed an increased incidence of leukemia in this group of
patients.
Increased incidences of leukemia, lung cancer, breast cancer, and thyroid
cancer have been observed in the Japanese survivors of the atomic bomb
attacks on Hiroshima and Nagasaki.
250 15. Radiation Biology