Combined treatment effects of irradiation and SN-38, an active metabolite of camptothecin derivative irinotecan, on the human tumor cell line PECA 4197

The in vitro combined effects of irradiation and SN-38, an active metabolite of irinotecan, on the human squamous cell carcinoma cell line PECA 4197 derived from a head and neck carcinoma were examined. Exponentially growing cell cultures were pretreated with SN-38 for 90 min, in the concentration of 0.005 and 0.5 μg/ml, respectively, and then irradiated. As a control, cells without pretreatment were also irradiated. The cell survival rate was determined using a conventional clonogenic survival assay. The enhanced effects of radiation-induced cell killing, depending upon the concentration of SN-38, were presented with a decrease of shoulder part or extrapolation number (n) of survival curve, corrected for the cytotoxicity of SN-38 alone. The value of D0 was unchanged after SN-38 pretreatment. These results suggested that the pretreatment with SN-38 inhibited potentially lethal damage repair in the cell line, leading to the potentiation of irradiation effects. (author)