Ref Robbins 7/e p323,9/e p324 Radiation, whatever its source (UV rays of sunlight, x-rays, nuclear fission, radionuclides) is an established carcinogen. Unprotected miners of radioactive elements have a 10-fold increased incidence of lung cancers. Follow-up study of survivors of the atomic bombs dropped on Hiroshima and Nagasaki disclosed a markedly increased incidence of leukemia--principally myelogenous leukemias--after an average latent period of about 7 years, as well as increased moality rates for thyroid, breast, colon, and lung carcino- mas. The nuclear power accident at Chernobyl in the former Soviet Union continues to exact its toll in the form of high cancer incidence in the surrounding areas. More recently, it is feared that radiation release from a nuclear power plant in Japan damaged by a massive eahquake and tsunami will result in significantly increased cancer incidence in the surrounding geographic areas. Therapeutic irradiation of the head and neck can give rise to papillary thyroid cancers years later. The oncogenic propeies of ionizing radiation are related to its mutagenic effects; it causes chromosome breakage, translocations, and, less frequently, point mutations. Biologically, double- stranded DNA breaks seem to be the most impoant form of DNA damage caused by radiation. The oncogenic effect of UV rays merits special mention because it highlights the impoance of DNA repair in car- cinogenesis. Natural UV radiation derived from the sun can cause skin cancers (melanomas, squamous cell carcino- mas, and basal cell carcinomas). At greatest risk are fair- skinned people who live in locales such as Australia and New Zealand that receive a great deal of sunlight. Non- melanoma skin cancers are associated with total cumula- tive exposure to UV radiation, whereas melanomas are associated with intense intermittent exposure--as occurs with sunbathing. UV light has several biologic effects on cells. Of paicular relevance to carcinogenesis is the ability to damage DNA by forming pyrimidine dimers This type of DNA damage is repaired by the nucleotide excision repair pathway. With extensive exposure to UV light, the repair systems may be overwhelmed, and skin cancer results. As mentioned earlier, patients with the inherited disease xeroderma pigmentosum have a defect in the nucleotide excision repair pathway. As expected, there is a greatly increased predisposition to skin cancers in this disorder.