Chromosomal and carcinogenic effects of sequential HZE and low-LET irradiations

All persons are exposed to a natural background of ionizing radiations with different spatial patterns of energy deposition resulting in differential biologic response. Astronauts, aircrew and radioactive contamination clean-up personnel are exposed to particularly complex radiation spectra. The current method for calculating radiation-induced exposure limits in mixed radiation environments is based on the linear summation of non-threshold risks, a methodology grounded in the premise that each component of the radiation field acts independently of the presence of other components.;The assumption of effect independence of in-vitro exposed samples was tested by evaluating the frequency of chromosome aberrations induced by sequential irradiation of immortalized human mammary epithelial cells with 1 GeV/nucleon 56Fe ions and 137Cs gamma-rays. Experimental response was found to be significantly less than calculated on the basis of effect independence, but only when 56Fe ions preceded the photon exposure. That there was order dependence is interpreted as evidence that response may not simply be a result of interactions between similar sublesions but rather may involve qualitatively different time-ordered parameters. The presence of this sub-additive response is phenomenologically similar to adaptive response, which had not been previously reported as a consequence to high-energy heavy ion irradiation.;Calculations based on effect independence predict a significantly greater average number and lifetime cumulative incidence of breast cancers in female Sprague-Dawley rats irradiated with both 56Fe ions and 250 MeV protons than was experimentally observed. This finding supports the hypothesis that the presence of non-additive response is not exclusively an in vitro phenomenon.;Results from an evaluation of mammary epithelial cell response induced in a rat cancer model are marginally consistent with the use of in vivo induced chromosome aberrations as a biomarker of breast cancer risk. There is also an apparent association between the two endpoints relating to dependence on radiation quality.;In conclusion, these data demonstrate that sequential exposures to both HZE and low-LET radiation may result in chromosomal and carcinogenic response that is inconsistent with effect independence. These results provide evidence that the linear summation of health risks from mixed HZE and low-LET radiation fields may not accurately reflect true risk.