Risk estimates for a variety of human cancers related to exposures to ionizing radiation are given in Table 12.1. Leading the list is leukemia, which has been the most frequent fatal cancer in a variety of situations. Perhaps most notable is the relatively high incidence of leukemia attribut- able to exposure to radiation from the atom bomb blasts of Hiroshima and Nagasaki (Shimizu et al., 1990). Leukemia was also a major result of x-ray treatment of ankylosing spondylitis in per- sons diagnosed between 1935 and 1957 in the United Kingdom (Weiss et al., 1995). Just as with the atom bomb survivors, the major risk of leukemia development occurred during the first 10 years following the first x-ray treatment, with risk decreasing rapidly to near zero thereafter. The incidence of chronic lymphocytic leukemia was not significantly affected by ionizing radiation, an effect also noted in the atomic bomb survivors (Ishimaru et al., 1979). Another dramatic rela- tionship between therapeutic radiation and induction in human cancer is seen with external radi- ation of the head, neck, and upper thorax and the induction of benign and malignant neoplasms of the thyroid gland. As shown in Figure 12.2, an almost linear dose-response of ionizing radia- tion and the developing thyroid cancer is noted in individuals radiated prior to age 15, whereas older individuals do not exhibit a similar risk relationship (cf. Schneider and Ron, 1997). This finding emphasizes the sensitivity of young individuals, with relatively high rates of cell replica- tion in a variety of tissues, during growing years. A similar relationship is also seen in the induc- tion of female breast cancer by ionizing radiation, as noted from the fact that essentially all cases of breast cancer resulting from radiation after the atom bomb blasts occurred in premenopausal women under age 40 (Goodman et al., 1994). A similar effect was noted in patients receiving radiotherapy for breast cancer in relation to risk of developing cancer in the unaffected breast. The risk of cancer development in the second breast was significantly increased among women less than 45 years of age who underwent radiation therapy (Boice et al., 1992). Furthermore, children irradiated for various therapeutic reasons also exhibited an increased risk of breast can- cer development (Modan et al., 1989; Hildreth et al., 1989). Another unfortunate example of radiation carcinogenesis in the human was that of workers who utilized pigments containing ra- dium salts to paint the dials of watches and airplane instruments. Many of the people operating such industries and instructing the workers did not believe the radium-containing paint to be hazardous. Thus, many of these workers absorbed the radioactive ions by mouth from the prac- tice of shaping a sharp point to the brush with their lips after dipping the brush in a solution of radium ions. Within 15 to 25 years after exposure, a significant number of these individuals de- veloped osteogenic sarcomas from the deposition of the radioactive radium in their bones. In addition, a large number of carcinomas of the cranial sinuses also occurred (Rowland and Lucas,1984). Many of the other radiogenic neoplasms listed in Table 12.1 as significantly associated with ionizing radiation exposure were identified in patients surviving the atom bomb blast. A
Figure 12.2 Dose-response curves for the development of thyroid cancer averaged from five cohort studies of childhood exposure (<15 years of age) and two studies of adult exposure (>15 years). (From Ron, 1996, with permission of the author and publisher.)
significant exception is the relatively rare phenomenon of postirradiation soft tissue sarcomas, which developed in a small percentage (less than 5%) of patients receiving relatively intensive doses of therapeutic radiation for a variety of reasons (Laskin et al., 1988; Brady et al., 1992; Bloechle et al., 1995). Osteogenic sarcomas and malignant fibrous histiocytomas predominate among these induced neoplasms, which usually have a very poor prognosis (Robinson et al.,1988).
Situational Exposures of Humans to Ionizing Radiation
As noted above, in a number of specific situations humans are exposed to excesses of ionizing radiation. The atom bomb blasts at Hiroshima and Nagasaki and medical therapy have ac- counted for a substantial part of such radiation.