Vulnerability of Feline T-Lymphocytes to Charged Particles

Abstract

ABSTRACT. An analysis of ionizing radiation-induced damage in peripheral lymphocytes has been employed to predict the prognosis of radiotherapy in terms of toxicity in normal tissues. Therefore, understanding the sensitivity of lymphocytes to high linear energy transfer (LET)-charged particles would be indispensable for utilizing charged particle therapy in veterinary medicine. However, the availability of such information is very limited. This study aimed to compare the radiosensitivity of feline T lymphocytes to γ-rays (0.2 keV/µm) and 4 different types of charged particles with LET values ranging from 2.8 to 114 keV/µm. It was observed that the relative biological effectiveness, inactivation cross-section, and isodose-induced apoptosis increased in an LET-dependent manner. On the other hand, no difference in apoptosis frequency was observed in the cells exposed to an isosurvival dose of all the radiation types tested. This is the first study that demonstrates the LET dependence of cell killing and apoptosis induction in feline T lymphocytes. Our results suggest that lymphocytes can be effectively used to predict the prognosis of charged-particle therapy in cat patients.

Magnetic resonance imaging of radiation-induced thymic atrophy as a model for pathologic changes in acute feline immunodeficiency virus infection

“…Histologic changes noted in the irradiated thymus were consistent with radiation-induced lymphocytolysis and overall loss of cellularity. 37,38 There was marked decrease in thymic size and alteration of the normal thymic pattern of organization, with reduced numbers of cortical lymphocytes, numerous apoptotic cells, increased numbers of histiocytes, and mild inflammation ( Fig 5). Although cell death and tissue destruction is achieved through different mechanisms in acutely FIV-infected cats, similar histologic changes can be noted.…”

Annexin V FITC conjugated as a radiation toxicity indicator in lymphocytes following radiation overexposure in radiotherapy programs

“…Apoptosis is a cell death process characterized by morphological and biochemical features occurring at different stages. [ 1 2 3 4 5 6 ] A critical stage of apoptosis involves the acquisition of surface changes by dying cells that eventually results in the recognition and uptake of these cells by phagocytes. Some changes occurred, such as the expression of thrombospondin binding sites, loss of sialic acid residues, and exposure of a phospholipid-like phosphatidylserine (PS) on the apoptotic cells’ membranes.…”

“…Cytogenetic analysis of peripheral blood lymphocytes (PBLs) can provide a precise estimation of the radiation dose received. [ 6 7 8 9 ]…”

“…[ 15 16 ] Theoretically, it enables resolution of doses smaller than the 50-100 mGy usually quoted as the lower limit for detection by scoring chromosome aberrations. [ 6 ] Recently, Boreham et al . have demonstrated that apoptosis-associated DNA unwinding in lymphocytes can be used as a potentially sensitive biological dosimeter at these doses.…”

The Bystander Response to Heavy-Ion Radiation: Intercellular Signaling Between Irradiated and Non-Irradiated Cells

“…Heavy ions are more genotoxic and cytotoxic to directly irradiated cells than low-LET photons like X-rays and γ-rays (Ando and Kase, 2009;Hamada, 2009;Hamada et al, 2010;Fokas et al, 2009). The mode of heavy ion-induced cell death/inactivation includes apoptosis, necrosis, autophagy, premature senescence, accelerated differentiation, together with delayed reproductive death in the progeny of irradiated cells (Al-Jahdari et al, 2009;Blakely and Chang, 2009;Hamada et al, 2006Hamada et al, , 2008aJinno-Oue et al, 2010;Kakizaki et al, 2006Kakizaki et al, , 2007Kawamura et al, 2009;Sora et al, 2008). In addition to LET, the heavy-ion response depends on ion species or ion track structure (Tsuruoka et al, 2005(Tsuruoka et al, , 2008.…”