Oxidative Stress In Liver Tissues In Hepatocellular Carcinoma Patients Receiving Transcatheter-arterial-Chemotherapy

Objective:to explore the status of oxidative stress and its association with transcatheter-arterial-chemotherapy(TAC)in liver tissues in hepatocellular carcinoma(HCC)patients.Materials and Methods:HCC patients were recruited from Guangxi, southern China,an endemic area of HCC.Cancer and surrounding tissues of a total 39(Group A and Group A')and 50(Group B and Group B')HCCs with and without pre-operative TAC respectively,were subjected to analysis.Fifteen non-HCC liver tissues were served as controls(Group C).Immunohistochemistry Streptavidin-biotinylated Peroxidase(S-P)method was used to detect cellular expression of p53 and p21^waf1/cip1and 8-hydroxydeoxydeguanosine (8-OHdG)levels in DNA in both cancer and surrounding tissues.Results:In tumor tissues,both 8-OHdG(F=101,P=0.039)and p53(t=-3.8, P＜0.001)levels in TAC group was lower than that in non-TAC group. Conversely p21^waf1/cip1expression was higher in TAC group(F=60.460, P＜0.001).There was strong association between 8-OHdG and p53 in cancer tissues in both cancer groups(r=-0.035,P＜0.001 in TAC group,and r=-0.083 P=0.003 in non-TAC group).The association between 8-OHdG and p21^waf1/cip1 was significant in non-TAC group(r=-0.105,P=0.002)but not in TAC group (r=-0.142,P=0.398).8-OHdG levels in cancer tissues were significantly higher than that in their surrounding tissues in both TAC(t=6.84,P＜0.001)and non-TAC(t=16.9,P＜0.001)groups.Yet there was no significant difference of p21^waf1/cip1levels between tumor and their surrounding tissues in either TAC (t=3.9,P=0.272)or non-TAC group(t=-6.488,P=0.075).p53 was not detected in para-tumor tissues.In Para tumor tissues,8-OHdG levels was the highest in non-TAC group, followed by TAC group and normal controls(F=39.85,P＜0.001).p21^way1/cip1 expression in normal controls was significantly higher than that in paratumor tissues in both TAC and non-TAC group(F=25.046,P＜0.001)yet the difference between the two latter was not significant(p=0.592).There was close association(r=0.405,P=0.004)of 8-OHdG levels between tumor and its surrounding tissues in non-TAC group.Yet no association of p21 (waf1/cip1)between tumor and its surrounding tissues in non-TAC group(r=0.254, P=0.075).There was no significant association between 8-OHdG and p21^{waf1 /cip1}levels in paratumor tissues in either TAC(r=-0.276,P=0.052)or non-TAC group(r=-0.231,P=0.107).Conclusions:We found in this study that there is alterations of oxidative stress status in both cancer and para-tumor tissues in HCCs after administration of chemotherapy.And a strong association between DNA damage biomarker and cell-cycle-regulators in these patients suggests distinct cellular response to oxidative challenge which might have clinical implications.