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Objective To investigate the changes of mutation of HPRT exposure to γ ray and benzo-pyrene,in order to try to find new differential diagnosis methods for cell injury induced by γ ray and benzo-pyrene.Methods Human peripheral blood samples from three persons were exposed to 60Co γ-rays at 10 different doses (0-5Gy) and benzo-pyrene at 6 different concentrations (0-10μg/ml),its DNA was isolated from white cell.The changes of mutation of HPRT exposure to γ ray and benzo-pyrene were detected by real-time quantitative PCR.Results The relationship between mutation frequency of HPRT and irradiation dose represents certain line correlation from 0~5 Gy,a linear regression equation(y=0.4298+0.0823x,P<0.01, R2=0.93) has been obtained using statistics regression analysis software,while,the relationship between mutation frequency of HPRT and different concentrations (0-10μg/ml) represents no statistical significance,which was obtained using statistics software as(y=0.4200+0.0019x,P>0.05,R2=0.450).There is an obvious influence on mutation frequency of exon 5 of HPRT induced byγray,while there is no obvious influence on mutation frequency of exon 5 of HPRT induced by benzo-pyrene,which may be a new differential diagnosis index in the future.