Radiation Interaction with Therapeutic Drugs and Cell Membranes

Abstract

This transient permeabilized state of the cell membrane, named the "cell electroporation" (CE) can be used to increase cells uptake of drugs that do not readily pass cell membrane, thus enabling their cytotoxicity. The anticancer drugs, such as bleomycin (BL) and cisplatin, are the most candidates for the combined use with ionizing and nonionizing radiation fields. The methods and installations for the cell electroporation by electron beam (EB) and microwave (MW) irradiation are presented. The viability tests of the human leukocytes under EB and MW exposure with/without the BL in the cell cultures are discussed.All biological membranes have a common general structure: each is a very thin film of lipid and protein molecules, held together mainly by noncovalent interactions. Certain membrane transport processes can be modified when the cell membrane bilayer viscosity is experimentally increased or decreased by applying different external physical energies such as EB and MW energy. The goal of our work was to find appropriate and necessary physical parameters of the applied EB and MW fields and cell cultures that perform destabilized cell membranes: more-permeable state of the cell membranes in order to increase cells uptake of drugs.EB and MW exposure experiments were carried out with originals experimental arrangements consisting mainly of an electron linear accelerator of 6.23 MeV and 75 mA and a 2.45 GHz generator of adjustable MW output power. Fig. 1 presents the effects of EB irradiation or/and bleomycin on leukocytes survival fraction: EB exposure of 0.5 Gy increases BL cytotoxicity by a factor of 1.39 for 7.5 |oM belomycin and 1.91 for 30 \xM bleomycin, respectively. Fig. 2 shows that 5 minutes and 25 minutes MW exposure at SAR of 25 W/kg increases BL (30 |aM) cytotoxicity by a factor of 1.28 and 1.7, respectively. CP899, Sixth International Conference of the Balkan Physical Union, edited by S. A. Cetin and I. Hikmet © 2007 American Institute of Physics 978-0-7354-0404-5/07/$23.00 ] Control sample ] Irradiated sample with EB of 0.5Gy ; o.8H | 0.2f| i o.o 7.5 Bleomycin (uJVl) FIGURE 1. The effects of EB irradiation or/and bleomycin on leukocytes survival fraction. Q^ 0 minutes MW irradiation Q^ 5 minutes MW irradiation ^H 25 minutes MW irradiation 0 fiL 30 ^L Bleomycin "S. 0.2 FIGURE 2. The effects of 5 and 25 min. MW irradiation or/and bleomycin upon leukocytes survival fraction. Transient and reversible permeabilization of the cell membrane can be induced by EB and MW exposure depending on the cell exposure level. 816