Enhancement of Hyperthermia on Radio-Sensitivity
Hyperthermia enhances radio-sensitivity of cancer cells when cancer cells are treated with combination of heat and radiation. This chapter describes usefulness of hyperthermia combined with radio-therapy and molecular mechanisms that enable hyperthermia t
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Enhancement of Hyperthermia on Radio-Sensitivity Ken Ohnishi
Abstract Hyperthermia enhances radio-sensitivity of cancer cells when cancer cells are treated with combination of heat and radiation. This chapter describes usefulness of hyperthermia combined with radio-therapy and molecular mechanisms that enable hyperthermia to enhance radio-sensitivity of cancer cells. Keywords Radio-sensitization • Cell cycle • DNA repair • O2 concentration
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Cell Cycle and Heat/Radio-Sensitivity
It is well known that radio-sensitivity of cancer cells is associated with cell cycle. In general, cancer cells are relatively sensitive to radiation in M-phase and a transitional phase from G1- to S-phase and late G2-phase. In contrast to this, cancer cells are relatively resistant to radiation in G1-phase and a transitional phase from late S-phase to early G2-phase. Such cell cycle-dependent radio-sensitivity is closely related to DNA repair systems. Double strand breaks (DSBs) of DNA induced by radiation are repaired by two major repair systems, nonhomologous end-joining (NHEJ) and homologous recombination (HR). DNA damages in G1 phase are repaired by NHEJ during G1-phase before the fixation of DNA damages in S-phase. This repair system leads cancer cells to resistant to radiation. The period of G1 phase varies among cell type. In cells derived from Chinese hamster, the period of G1 phase is very short. Thus, the radio-resistance in G1 phase is not observed in those cells [1]. In late G1 phase and early S-phase, DNA damages of cancer cells are fixed during DNA replication in S-phase and the fixation of DNA damages causes cell death. The cell death results in relatively higher radiosensitivity of cancer cells in those phases. HR functions in late S-phase to early G2-phase and DNA repair by HR causes radio-resistance of cancer cells. M-phase shows dynamic morphological changes of cells such as disappearance of nuclear membrane and condensation of chromosome. The morphological changes are
K. Ohnishi (*) Department of Biology, Center for Humanity and Sciences, Ibaraki Prefectural University of Health Sciences, 4669-2 Ami, Inashiki-gun, Ibaraki 300-0394, Japan e-mail: [email protected] © Springer Science+Business Media Singapore 2016 S. Kokura et al. (eds.), Hyperthermic Oncology from Bench to Bedside, DOI 10.1007/978-981-10-0719-4_8
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closely related to radiation-induced lethal DNA damages. Thus, cancer cells are relatively radio-sensitive in M-phase. Heat sensitivity of cancer cells is also associated with cell cycle. It is reported that nuclear fragmentation and premature chromosome condensation are induced by heat in S-phase cells [2]. The activity of DNA polymerase α functioning in DNA replication in S-phase is depressed by heat [3]. Thus, heat sensitivity is relatively high in cancer cells heated in S-phase. Hyperthermia is effective for growing tumors because they contain many cells of S-phase. The cell cycle dependent heat sensitivity suggests that there are various molecules regulating cell response after h
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