title: Radiosensitivity in multidrug-resistant and cisplatin-resistant human carcinoma cell lines.
abstract: The radiosensitivity of a multidrug-resistant (MDR) clone and a cisplatin-resistant clone was compared with that of their parental chemosensitive cell lines. The LoVo cell line was derived from a human colon carcinoma, and LoVo-R was the MDR clone. The MDR phenotype is attributable to an increased drug efflux mediated by the P-glycoprotein and involves several classes of structurally unrelated drugs. The 2008 cell line was derived from a human ovary carcinoma and C13 was the cisplatin-resistant clone. Reduced cisplatin accumulation and elevated plasma membrane potential partially account for the drug resistance of C13 cells. The chemoresistance of LoVo-R and C13 cells was confirmed by cytotoxicity tests consisting of 24-hour paclitaxel and 1-hour cisplatin incubation, respectively. The radiosensitivity was evaluated by a clonogenic test. The dose-reducing cell survival fraction from 1 to 0.37 (D(0)), the quasi-threshold dose (Dq), and the survival fraction (SF) after 2 or 4 Gy were determined for each cell line. D(0), Dq, and SF(2) were 1.3 +/- 0.4 Gy, 2.1 +/- 0.6 Gy, and 43 +/- 4% for the LoVo cell line and 1.0 +/- 0.2 Gy, 1.7 +/- 0.4 Gy, and 45 +/- 8%, respectively, for the LoVo-R cell line. D(0), Dq, and SF(4) were 1.7 +/- 0.3 Gy, 3.1 +/- 0.4 Gy, and 43 +/- 12% for 2008 cells and 2.6 +/- 0.5 Gy, 4.3 +/- 0.6 Gy, and 53 +/- 11%, respectively for C13 cells. No significant differences were found between LoVo and LoVo-R cells, whereas C13 cells showed a significantly greater D(0,) Dq, and SF(4) than 2008 cells (p <0.05). Incubation of 2008 and C13 cells with subcytotoxic buthionine (BSO) before and after irradiation partially restored C13 radiosensitivity. In fact, D(0) dropped from 2.8 +/- 0.1 to 2.0 +/- 0.3 Gy in C13 cells with and without BSO, whereas it was 1.9 +/- 0.2 Gy in 2008 cells in the absence and presence of BSO. The total glutathione content (GSH) of C13 cells was 1.5-fold higher than that of 2008 cells. BSO treatment caused a partial depletion of GSH in 2008 and C13 cells, but their radiosensitivity did not change accordingly.
authors.affiliation: School of Radiotherapy, University of Padua, Padua, Italy. gigante_marco@hotmail.com
authors.forename: Marco
authors.initials: M
authors.lastname: Gigante
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Toffoli
authors.forename: Antonella
authors.initials: A
authors.lastname: Bertola
authors.forename: Gabriella
authors.initials: G
authors.lastname: Biscontin
authors.forename: Andrea
authors.initials: A
authors.lastname: Dassie
authors.forename: Giuseppe D
authors.initials: GD
authors.lastname: Zanelli
authors.forename: Enzo
authors.initials: E
authors.lastname: Zanin
authors.forename: Mauro G
authors.initials: MG
authors.lastname: Trovò
authors.forename: Pier Carlo
authors.initials: PC
authors.lastname: Muzzio
mesh_terms: D045744:Cell Line, Tumor / Q000187:drug effects* / Q000528:radiation effects*; D002470:Cell Survival; D002945:Cisplatin; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005978:Glutathione; D006801:Humans; D008715:Methionine / Q000031:analogs & derivatives*; D011836:Radiation Tolerance; D014410:Tumor Stem Cell Assay
chemical_list: C042415:buthionine; D008715:Methionine; D005978:Glutathione; D002945:Cisplatin