Number of Fe Ion Traversals Through a Cell Nucleus for Mammalian Cell Inactivation Near the Bragg Peak

Abstract

HeLa and CHO-K1 cells were irradiated with Fe ions (1.14 MeV/nucleon) near the Bragg peak to determine how many ion traversals through a cell nucleus are necessary to induce cell inactivation. The ion traversals through a cell nucleus were visualized by immunostaining the phosphorylated histone H2AX (gamma-H2AX), as an indicator of DNA double strand breaks (DSBs), to confirm that DSBs are actually induced along every Fe ion traversal through the nucleus. The survival curves after irradiation with Fe ions decreased exponentially with the ion fluence without a shoulder. The inactivation cross sections calculated from the slope of the survival curves and the standard errors were 96.9 +/- 1.8 and 57.9 +/- 5.4 microm2 for HeLa and CHO-K1 cells, respectively, corresponding to 0.442 and 0.456 of the mean value of each cell nucleus area. Taking the distribution of the cell nucleus area into consideration with an equation proposed by Goodhead et al. (1980), which calculates the average number of lesions per single ion track through the average area of a sensitive organelle (mainly nucleus), these two ratios were converted to 0.705 and 0.659 for HeLa and CHO-K1 cells, respectively. These ratios were less than one, suggesting that the average numbers of lethal hits per cell produced by a single ion traversal were less than one. We thus considered two possible explanations for ion traversals of more than one, necessary for cell inactivation.

The Mayo Clinic Florida Microdosimetric Kinetic Model of Clonogenic Survival: Application to Various Repair-Competent Rodent and Human Cell Lines

“…(3) If also no cross-sectional area measurements are available, we propose a novel phenomenological correlation between the mean DNA content of an asynchronized population Γ and the mean radius of the cell nucleus R n for asynchronized cells. In this regard, Figure 12 shows the mean radius of the cell nucleus R n plotted as a function of the mean DNA content of 22 different asynchronized cell lines (details on the published morphological data [ 9 , 57 , 58 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ] can be found in Table S1 in the Supplementary Materials ). A phenomenological correlation was established between the two quantities as described in Equation (10).…”

Lethal DNA damages caused by ion-induced shock waves in cells

“…15(A,B) are obtained with the values A n (V79) = 88 µm 2 and A n (CHO) = 127 µm 2 taken, respectively, from the experimental studies [73,74]. As it was reported by Konishi et al [74] the distribution of nucleus areas for the CHO cells is characterized by a rather broad Gaussian-like profile, and the measured nucleus areas varies from about 80 µm 2 up to 160 µm 2 with the average value of 127 µm 2 . The variation of the calculated cell survival probabilities related to the variation of the nucleus size is illustrated in Fig.…”

“…15 by the shaded areas. Note also that no data on the experimental uncertainties of the measured cell survival probabilities were provided in the earlier experimental studies [73,74]. Therefore, we have estimated the characteristic uncertainties for the cells irradiated at doses up to about 10 Gy based on the typical experimental uncertainties arising in such measurements with carbon ions (Fig.…”

Biological studies using mammalian cell lines and the current status of the microbeam irradiation system, SPICE

“…Culture conditions were described previously [16,29]. Cells were stained with 1 lM Hoechst 33258 before being irradiated to determine the cell positions in the dish (see Fig.…”

“…We visualized the DSBs induced by the traversals of protons through the cell nucleus using phosphorlylated histone, H2AX (c-H2AX), as a marker for DNA DSBs [29,30]. CHO-K1 cells were prepared and cultured on the cell dish 24 h before irradiation.…”