Tumorigenic Potential of High-Z, High-LET Charged-Particle Radiations

Abstract

The potential for radiogenic neoplasia from charged-particle irradiation has been estimated using the Harderian gland of the mouse as a test system. Particles ranging in Z from Z = 1 (proton) to Z = 41 (niobium), in energy from 228 to 670A MeV, and in LET from 0.4 to 464 keV/microns were produced at the Lawrence Berkeley Laboratory BEVALAC. Expression of the tumorigenic potential of the initiated cells was enhanced by hormones from isogeneic grafts of pituitaries. The goal of the studies was to estimate the initial slope of the relationship between increased tumor prevalence at 16 months after irradiation and the dose received. Initial slopes were measured with good precision for 60Co gamma rays and the Bragg plateau beams of 228A MeV 4He ions, 600A MeV 56Fe ions, and 350A MeV 56Fe ions. The ratio of the initial slope for these ions to that of 60Co gamma rays give an estimate of the maximum RBE for radiogenic neoplasia. These values were 2.3 for the 4He ions, 40 for 600A MeV 56Fe, and 20 for 350A MeV 56Fe. In the studies reported here the prevalence of tumors as the result of pituitary isografts was not enhanced after irradiation with 56Fe ions. It remains to be seen how effective pituitary isografts are for enhancement of radiogenic neoplasia from other ions at different LET values. A risk analysis was undertaken using particle fluence rather than dose as the independent variable. This analysis provides a value for a "cross section" expressed in microns 2. This parameter expresses as the increase in proportion of mice with one or more Harderian gland tumors per unit increase in particle fluence. The plot of the cross section (risk coefficient) as a function of LET is monotonic, with no clear evidence of a maximum value of the risk coefficient for even the highest LET particle used.

Heavy ion carcinogenesis and human space exploration

“…There are gaps in knowledge related to space radiation and carcinogenic processes that must be addressed to validate cancer projection models 58 ( Figure 4). Animal studies generally demonstrate that HZE nuclei have a higher carcinogenic effectiveness than low-LET radiation [59][60][61][62] , but RBE values are difficult to quantify because of statistical uncertainties, which in many experiments prevents a conclusion on response at low dose and dose-rates. The large number of radiation types and energies in space precludes an extensive study of tumor types in different strains of mice with different ion/dose regimes.…”

Radiation as a Risk Factor for Cardiovascular Disease

“…For humans, there is no information available as to the relative biological effectiveness of these particles in the heart. In studies on other organs, the relative biological effectiveness of high-energy heavy ions in mice and rats for carcinogenesis in skin and Harderian or mammary glands can be as high as 25-40 after doses < 1 Gy (5,16,30). Thus, by extrapolation, the radiation dose from ions of iron, helium, and possibly protons needed to increase the risk factors for cardiovascular disease is likely to be considerably less than for g-rays.…”

Combinatorial DNA Damage Pairing Model Based on X-Ray-Induced Foci Predicts the Dose and LET Dependence of Cell Death in Human Breast Cells

“…Risk uncertainties for space radiation tumorigenesis are typically inferred from low-LET risk using a quality factor or RBE (relative biological effectiveness) [2]. RBE as high as 40 have been reported for Harderian gland tumors detected in mice exposed to 600 MeV/n Fe [3]. In other words, it takes 40 times more dose of X-rays to lead to the same tumor incidence than with HZE Fe.…”