The Study Of The Biomarkers For Cytogenetic Damage Induced By Antineoplastic Chemotherapy In Ovarian Cancer Patients

Objective:To study the variety of SCE frequency,hprt mutation and MN frequencies in peripheral blood lymphocytes(PBL)of patients with ovarian cancer during antineoplastic chemotherapy supervision;the applicability of SCE,hprt mutation and MN assays as cyto genetic markers for evaluating in vivo chemotherapy induced chromosome damage. Methods:Collected peripheral blood of 19 ovarian cancer patients in stageâ…¢ before and after every course of chemotherapy(PAC scheme) after the cytoreductive surgery ,the SCE assay,hprt gene locus mutation and cytokinesis-blocked MN assays were applied.At the same time points,the routine whole blood count tests were taken. Result:1. During the chemotherapy,the average SCE frequencies significantly increased after every course chemotherapy(P<0.001).Compared with the basal line,SCE frequencies at the beginning of all courses after the chemotherapy beginning had a significant increase(P<0.05).So did the dates at the end of every courses.The SCEf in PBL increased linearly with the DDP dose per square metre as Y=0.0743X+6.226, r=0.985 (P<0.01) , so they had a significant correlation.2. During the 1-4 coures, the average MNf increased after every course chemotherapy,but not significantly.MNf at the end of every courses increasedgradually and were markedly higher than that in the basal line .MNf also had a significant correlation, with the chemotherapeutics dose,r=0.948(P<0.05),the regression equation was Y=0.0768X+l 3.862.3. Hprt mfs after every course was elevated gradually during the first three courses,then decreased after the forth course.Hprt mfs after 2,3 and 4 course were markedly higher than that of the basal line level.4. SCEf and MNf assessed after all courses of therapy correlated closely to each other, r=0.977(P<0.0l).5. Marrow suppress induced by chemotherapy and the three biomarkers:The increase of SCEf correlated negatively with the decrease of white blood cell counts in PBL,r=-0.43(.P<0.01). There is no correlation between the decrease of white blood cell counts in PBL and MNf.Neither did the hprt mf. Conclussions:l.SCEf after every course increased gradually and the frequency of SCE after every course treatment increased respectively with the accumulating of DDP dose per square metre,that is,there was a good dose-effect manner between SCEfs and chemotherapeutics such as DDP.lt was suggested that chemotherapy induced human chromosomes damages which piled up with the treatment proceeding.Every course chemotherapy could induce significant increase in SCE;After a chemotherapy interval(21-28d),SCEf decreased but never back to the basal level before the next course treatment.So SCE is very sensitive to chemotherapy.The interval periods were helpful to repair DNA damages,although the repairs were incomplete.2.The average MNf increased after every course chemotherapy,but not significantly.MNf also had a significant correlation^ with the chemotherapeutics dose. So MN assay could determine the cytogenetic damage induced by chemotherapy.