Radiobiological experiments for carbon ion prostate cancer therapy: Interplay of normal and tumor cells in co-culture and measurement of the oxygen enhancement ratio

• Main Author: von Neubeck, Cläre
• Format: Others
• Language: English; en
• Published: 2009
• Online Access: https://tuprints.ulb.tu-darmstadt.de/1973/1/Cl%C3%A4re_PhD.pdf; von Neubeck, Cläre <http://tuprints.ulb.tu-darmstadt.de/view/person/von_Neubeck=3ACl=E4re=3A=3A.html> (2009): Radiobiological experiments for carbon ion prostate cancer therapy: Interplay of normal and tumor cells in co-culture and measurement of the oxygen enhancement ratio.Darmstadt, Technische Universität, [Ph.D. Thesis]

Co-culture models are helpful to examine cell to cell interactions in vitro and to assess the cross-communication between two particular cell populations. Co-culture systems partially reflect the complex in vivo situation: in this study an in vitro co-culture model of prostate cancer cells {(Dunning R-3327-AT-1)} and small intestine cells {(intestinal epithelium cell line 6)} of the rat was established to simulate the carbon ion treatment of prostate cancer patient at GSI. Both cell lines were characterized in mono-cultures for their radio-biological response against 250 kVp x-rays and carbon ions of 270 MeV/u, 100 MeV/u, and 11.4 MeV/u, respectively. The parameters of the linear quadratic model, alpha and beta, for cell survival curves were determined as well as the relative biological effectiveness {(RBE)}. The measured RBE values were compared to calculations of the local effect model and were in agreement with the calculations. The RBEalpha increased stronger for the more radio-resistant prostate cancer cell line than for the epithelium cell line. The survival of unirradiated and irradiated cells from co-culture {(250 kVp x-rays, 100 MeV/u and 11.4 MeV/u carbon ions)} was compared to mono-cultures under the same conditions. The measured effects were attributed to irradiation independent as well as irradiation dependent factors. To study these effects, the inflammatory cytokines TGFbeta, TNFalpha, and IL-2 were analyzed, but their secretion was independent of radiation. To study the problem of hypoxic cells in tumor treatment a hypoxia chamber was developed in which cells were grown under defined oxygen status. Prostate cancer cells were irradiated with 250 kVp x-rays and carbon ions with a mean LET of 100 keV/µm under oxic and hypoxic conditions. The oxygen enhancement ratios for 10\% survival were found to be OER 2.35 for x-rays and 1.5 for carbon ions. The results of the co-culture model and the experiments under defined oxygen status are discussed in relation to ongoing prostate cancer therapy.