Response of human lymphocytes to proton radiation of 60 MeV compared to 250 kV X-rays by the cytokinesis-block micronucleus assay

Abstract

Particle radiotherapy such as protons provides a new promising treatment modality to cancer. However, studies on its efficacy and risks are relatively sparse. Using the cytokinesis-blocked micronucleus assay, we characterized response of human peripheral blood lymphocytes, obtained from health donors irradiated in vitro in the dose range: 0-4. 0 Gy, to therapeutic proton radiation of 60 MeV from AIC-144 isochronous cyclotron, by studying nuclear division index and DNA damage and compared them with X-rays. Peripheral blood lymphocytes show decreased ability to proliferate with increasing radiation doses for both radiation types, however, in contrast to X-rays, irradiation with protons resulted in a higher proliferation index at lower doses of 0.75 and 1.0 Gy. Protons are more effective in producing MN at doses above 1.75 Gy compared to X-rays. Dose-response curves for micronucleus incidence can be best described by a cubic model for protons, while for X-rays the response was linear. The differences in the energy spectrum and intracellular distribution of energy between radiation types are also apparent at the intracellular distribution of cytogenetic damage as seen by the distribution of various numbers of micronuclei in binucleated cells. Our studies, although preliminary, further contribute to the understanding of the mechanistic differences in the response of HPBL in terms of cellular proliferation and cytogenetic damage induced by protons and X-rays as well as intra-cellular distribution of energy and thus radiobiological effectiveness.

Keywords: Cytokinesis-block micronucleus assay; Human lymphocytes; Micronuclei frequency; Nuclear division index; Proton beam; X-rays.