Dose-thresholds for alpha-radiation induced cancer risk: absence of risk following small alpha-emitting radionuclide intakes

The recent introduction of radiopharmaceuticals containing a-emitting radionuclides has introduced an imperative to increase our understanding of the risks of induced secondary cancers in patients that have received treatments and of new cancers in staff that are occupationally exposed to α-emitters within the work place. A new paradigm for a-radiation induced cancer is proposed that builds on a mechanism of carcinogenesis that has been published to explain the lung carcinogenic properties of asbestos. According to this mechanism lung cancer is a consequence of necrotic cell death and the subsequent production of a chronic inflammatory response. It is suggested that DNA damage to cells, that could subsequently produce tumours, is a consequence of their exposure to reactive oxygen species and free radicals produced by the inflammatory process. This is in marked contrast to current assumptions that suggest that cancer is a result of random single and double strand breaks in DNA produced directly by the radiation. If the induction of chronic inflammation is required for cancer induction then is hypothesised that low α-doses to tissues will result in the killing of too few cells to produce chronic inflammation and cancer. This hypothesis was tested by a re-examination of dose-response in 22, randomly selected, published studies of the toxicity of α-emitting radionuclides in man, dogs, rats and mice. The results showed that below an average tissue dose of 0.51Gy, with 95% CI of 4.4Gy and 0.06Gy, no cancers were produced following radionuclide intakes. It is concluded that provided tissue a-doses are kept below threshold values the use of α-radiopharmaceuticals will neither result in the production of cancers in non-target tissues nor present a cancer risk to health workers. (author)