A number of the points made about chemical carcinogenesis are also true for radiation-induced
carcinogenesis. Both X-rays and ultraviolet (UV) radiation, for example, produce damage to DNA.
As with chemical carcinogens, this damage induces DNA repair processes, some of which are
error prone and may lead to mutations. The developmentofmalignanttransformationincultured
cells after irradiation requires cell proliferation to ‘‘fix’’ the initial damage into a heritable change and
then to allow clonal proliferation and expression of the typical transformed phenotype.105 Fixation
appears to be complete after the first postirrad transformation requires an additional 12 rounds
Measured cancer risk at high dose Increasing incidence of tumors Increasing. Linear curve. Curves with this appearance
are not usually found experimentally in dose– response assays, and the idea that a dose–response
curve could take such a form is now considered obsolete. (From America’s War on ‘‘Carcinogens’’: Reassessing
the Use of Animal Tests to Predict Hum Increasing dose . Nonlinear threshold. (From America’s War on ‘‘Carcinogens’’: Reassessing the Use of Animal Tests to Predict Human Cancer Risk, p. 53, with permission.) of cell division. Thus, as in the case of chemical carcinogenesis, a promotion phase is required for
full expression of the initiated malignant alteration. Moreover, when low doses of chemical
carcinogens and X-rays are used together, these two types of agents act synergistically to produce
malignant transformation.105
When cells are exposed to UV light in the 240 to 300 nm range, the bases acquire excited energy
states, producing photochemical reactions between DNA bases (reviewed in Reference 106). The principal products in DNA at biologically relevant doses of UV light are cyclobutane dimers formed between two adjacent pyrimidine bases in the DNA chain. Both thymine–thymine and thymine–cytosine dimmers are formed. That formation of these dimers is linked to mutagenic events .
Heavy exposure to sunlight induces similar changes in human skin, and the degree of exposure
to sunlight is closely related to the incidence of skin cancer. Whether continuing exposure to UV rays in sunlight is the promoting agent in skin cancer or additional promoting events are required is not clear, but it seems that UV irradiation is a complete carcinogen, just as some chemicals are—that is, it has both initiating and promoting activities. Patients who cannot efficiently repair UV-induced damage,
such as those with xeroderma pigmentosum, have a much higher risk of developing malignant skin tumors.
