Quantitative comparisons of cancer induction in humans by internally deposited radionuclides and external radiation.

PURPOSE: To compare quantitative estimates of lifetime cancer risk in humans for exposures to internally deposited radionuclides and external radiation. To assess the possibility that risks from radionuclide exposures may be underestimated.
MATERIALS AND METHODS: Risk estimates following internal exposures can be made for a small number of alpha-particle-emitting nuclides. (1) Lung cancer in underground miners exposed by inhalation to radon-222 gas and its short-lived progeny. Studies of residential (222)Rn exposure are generally consistent with predictions from the miner studies. (2) Liver cancer and leukaemia in patients given intravascular injections of Thorotrast, a thorium-232 oxide preparation that concentrates in liver, spleen and bone marrow. (3) Bone cancer in patients given injections of radium-224, and in workers exposed occupationally to (226)Ra and (228)Ra, mainly by ingestion. (4) Lung cancer in Mayak workers exposed to plutonium-239, mainly by inhalation. Liver and bone cancers were also seen, but the dosimetry is not yet sufficiently good enough to provide quantitative estimates of risks. Comparisons can be made between risk estimates for radiation-induced cancer derived for radionuclide exposure and those derived for the A-bomb survivors, exposed mainly to low-LET (linear energy transfer) external radiation. Data from animal studies, using dogs and rodents, allow comparisons of cancer induction by a range of alpha- and beta-/gamma-emitting radionuclides. They provide information on relative biological effectiveness (RBE), dose-response relationships, dose-rate effects and the location of target cells for different malignancies.
RESULTS: For lung and liver cancer, the estimated values of risk per Sv for internal exposure, assuming an RBE for alpha-particles of 20, are reasonably consistent with estimates for external exposure to low-LET radiation. This also applies to bone cancer when risk is calculated on the basis of average bone dose, but consideration of dose to target cells on bone surfaces suggests a low RBE for alpha-particles. Similarly, for leukaemia, the comparison of risks from alpha-irradiation ((232)Th and progeny) and external radiation suggest a low alpha RBE; this conclusion is supported by animal data. Risk estimates for internal exposure are dependent on the assumptions made in calculating dose. Account is taken of the distribution of radionuclides within tissues and the distribution of target cells for cancer induction. For the lungs and liver, the available human and animal data provide support for current assumptions. However, for bone cancer and leukaemia, it may be that changes are required. Bone cancer risk may be best assessed by calculating dose to a 50 micro m layer of marrow adjacent to endosteal (inner) bone surfaces rather than to a single 10 micro m cell layer as currently assumed. Target cells for leukaemia may be concentrated towards the centre of marrow cavities so that the risk of leukaemia from bone-seeking radionuclides, particularly alpha emitters, may be overestimated by the current assumption of uniform distribution of target cells throughout red bone marrow.
CONCLUSIONS: The lifetime risk estimates considered here for exposure to internally deposited radionuclides and to external radiation are subject to uncertainties, arising from the dosimetric assumptions made, from the quality of cancer incidence and mortality data and from aspects of risk modelling; including variations in baseline rates between populations for some cancer types. Bearing in mind such uncertainties, comparisons of risk estimates for internal emitters and external radiation show good agreement for lung and liver cancers. For leukaemia, the available data suggest that the assumption of an alpha-particle RBE of 20 can result in overestimates of risk. For bone cancer, it also appears that current assumptions will overestimate risks from alpha-particle-emitting nuclides, particularly at low doses.