%0 Journal Article %T X-Ray Induced Mutation Frequency at the <i>Hypoxanthine Phosphoribosyltransferase</i> Locus in Clinically Relevant Radioresistant Cells %A Yoshikazu Kuwahara %A Mehryar Habibi Roudkenar %A Yusuke Urushihara %A Yohei Saito %A Kazuo Tomita %A Amaneh Mohammadi Roushandeh %A Tomoaki Sato %A Akihiro Kurimasa %A Manabu Fukumoto %J International Journal of Medical Physics,Clinical Engineering and Radiation Oncology %P 377-391 %@ 2168-5444 %D 2017 %I Scientific Research Publishing %R 10.4236/ijmpcero.2017.64034 %X To elucidate the molecular mechanisms underlying cellular radioresistance, clinically relevant radioresistant cell lines were established via long-term exposure to X-rays with stepwise dose escalation. Established cells continue to proliferate despite exposure to 2 Gy X-rays/day for more than 30 days, a standard protocol in cancer radiotherapy. DNA repair fidelity in radioresistant and the parental cells by evaluating the mutation frequency at the <i>hypoxanthine phosphoribosyltransferase</i> (<i>HPRT</i>) locus after exposure to X-rays was determined. Mutation spectrum at the <i>HPRT</i> locus was examined by multiplex polymerase chain reaction. Rejoining kinetics of X-ray-induced DNA double strand breaks (dsbs) was evaluated by the detection of phosphorylated histone H2AX (¦ÃH2AX) after X-irradiation. The fold increase in the <i>HPRT</i> mutation frequency due to acute radiation was similar between radioresistant and the parental cell lines. However, fractionated radiation (FR) consisting of 2 Gy X-rays/day increased the mutation frequency at the <i>HPRT</i> locus in parental but not in %K Clinically Relevant Radioresistant (CRR) Cell %K Hypoxanthine Phosphoribosyltransferase (HPRT) %K Mutation Frequency %K Phosphorylated Histone H2AX (¦ÃH2AX) %K X-Rays %U http://www.scirp.org/journal/PaperInformation.aspx?PaperID=80133