title: 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.
authors.affiliation: Department of Experimental Physics of Complex Systems, The H. Niewodniczański Institute of Nuclear Physics Polish Academy of Sciences, Kraków, Poland. Electronic address: justyna.miszczyk@ifj.edu.pl.
authors.forename: Justyna
authors.initials: J
authors.lastname: Miszczyk
authors.affiliation: Department of Experimental Physics of Complex Systems, The H. Niewodniczański Institute of Nuclear Physics Polish Academy of Sciences, Kraków, Poland; Marian Smoluchowski Institute of Physics, Jagiellonian University, Kraków, Poland.
authors.forename: Kamila
authors.initials: K
authors.lastname: Rawojć
authors.affiliation: Department of Experimental Physics of Complex Systems, The H. Niewodniczański Institute of Nuclear Physics Polish Academy of Sciences, Kraków, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Panek
authors.affiliation: Cyclotron Center Bronowice, Proton Radiotherapy Group, The H. Niewodniczański Institute of Nuclear Physics Polish Academy of Sciences, Kraków, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Swakoń
authors.affiliation: National Cancer Institute, National Institutes of Health, Bethesda, USA.
authors.forename: Pataje G
authors.initials: PG
authors.lastname: Prasanna
authors.affiliation: Cyclotron Center Bronowice, Proton Radiotherapy Group, The H. Niewodniczański Institute of Nuclear Physics Polish Academy of Sciences, Kraków, Poland.
authors.forename: Marzena
authors.initials: M
authors.lastname: Rydygier
mesh_terms: D000328:Adult; D002467:Cell Nucleus / Q000528:radiation effects*; D049109:Cell Proliferation / Q000528:radiation effects; D002478:Cells, Cultured; D048749:Cytokinesis / Q000528:radiation effects*; D004249:DNA Damage; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000528:radiation effects*; D008297:Male; D015162:Micronucleus Tests; D008875:Middle Aged; D011522:Protons; D011829:Radiation Dosage
chemical_list: D011522:Protons
keywords: Cytokinesis-block micronucleus assay; Human lymphocytes; Micronuclei frequency; Nuclear division index; Proton beam; X-rays