Radiation Carcinogenesis in Experimental Animals and Its Implications for Radiation Protection

Abstract

Cancer induction is generally considered to be the most important somatic effect of low doses of ionizing radiation. It is therefore of great concern to assess the quantitative cancer risk of exposure to radiations of different quality and to obtain information on the dose-response relationships for carcinogenesis. Tissues in the human with a high sensitivity for cancer induction include the bone marrow, the lung, the thyroid and the breast in women. If the revised dosimetry estimates for the Japanese survivors of the atomic bomb explosions are correct, there is no useful data base left to derive r.b.e. values for human carcinogenesis. As a consequence, it will be necessary to rely on results obtained in biological systems, including experimental animals, for these estimates. With respect to radiation protection, the following aspects of experimental studies on radiation carcinogenesis are of relevance: Assessment of the nature of dose-response relationships. Determination of the relative biological effectiveness of radiations of different quality. Effects of fractionation or protraction of the dose on tumour development. For the analysis of tumour data in animals, specific approaches have to be applied which correct for competing risks. These methods include actuarial estimates, non-parametric models and analytical models. The dose-response curves for radiation-induced cancers in different tissues vary in shape. This is exemplified by studies on myeloid leukaemia in mice and mammary neoplasms in different rat strains. The results on radiation carcinogenesis in animal models clearly indicate that the highest r.b.e. values are observed for neutrons with energies between 0.5 and 1 MeV. On the basis of such results it might be concluded that the maximum quality factor of 10 for neutrons should be increased. Based on current evidence, an increase by a factor of 2 to 3 seems more realistic than a tenfold rise. The diversity of dose-response relationships point to different mechanisms involved in the induction of different tumours in various species and even in different strains of the same species.

Relative biological effectiveness (RBE), quality factor (Q), and radiation weighting factor (wR)

“…The same group estimated RBE for both fibroadenoma and adenocarcinomas to be about 10, but in combination with diethylstilbestrol, RBE for adenocarcinomas and all mammary tumours rose to about 100 (Shellabarger et al, 1982). Broerse et al (1985Broerse et al ( , 1991 reported an RBE of 7 for 0.5 MeV neutrons vs x rays in a study of mammary fibroadenomas in a different colony of Sprague-Dawley rats than that used by Shellabarger et al (1980), and an RBE of 15 for adenocarcinomas in WAG/Rij rats.…”

Neoplasia and Proliferative Disorders of Nonhuman Primates

“…The effects of UV radiation in nonhuman primates is not well known, although UV light in combination with other carcinogens applied to the skin of rhesus macaques has been linked to the development of skin tumors, including basal cell tumors (Palotay et al, 1976). Studies have been conducted using nonhuman primates to determine the effects of whole body irradiation, as well as the effects of therapeutic measures such as bone marrow transplantation (Broerse et al, 1985). In a study of the effects of simulated space irradiations, 1000 rhesus monkeys were exposed to various types of whole body irradiation using protons, electrons, neutrons, and X-rays (Splitter et al, 1973).…”

Radiation‐induced lymphoid tumors and radiation lethality are inhibited by combined treatment with small doses of zinc aspartate and wr 2721

“…A benefit of chemical radioprotection would be the inhibition of radiation carcinogenesis. Models for experimental tumor induction by ionizing radiation are not entirely satisfactory because of their long duration, while often only a moderate rate of tumor development is achieved (Broerse et al, 1985;Coggle, 1988;Covelli et al, 1988;Fry, 1981;Mole, 1984;Twentyman et al, 1980;Ullrich, 1983). Little work has been directed towards the question of how radioproteetive agents influence radiation carcinogenesis in vivo.…”