Pre-exposure of human squamous carcinoma cells to low-doses of gamma-rays leads to an increased resistance to subsequent low-dose cisplatin treatment

Abstract

Purpose: To investigate low-dose hypersensitivity to cisplatin and increased resistance at higher doses of cisplatin for the human squamous carcinoma cell line SCC-25 and its cisplatin-resistant derivative SCC-25/CP, and to examine the effects of pre- and post-treatment of SCC-25 cells with low-doses of gamma-rays on their resistance to cisplatin. Materials and methods: SCC-25 and SCC-25/CP cells were treated with various cisplatin concentrations (0.1 to 20 mu m for 1h) and assayed for survival using a conventional colony assay. For SCC-25, various doses of gamma-rays (5cGy to 2.5Gy) were given either 10 or 60min before the cisplatin challenge dose as well as either 10 or 60min after the cisplatin challenge dose. Results: Low-dose (0.5, 0.75 and 1 mu m for 1h) hypersensitivity to cisplatin and increased resistance at higher doses was detected for the SCC-25 cell line, but not for its cisplatin-resistant derivative, SCC-25/CP. Pretreatment of SCC-25 cells with an acute low-dose of 5, 25cGy or 1Gy gamma -rays given 60min before a low-dose cisplatin challenge (0.1 and 1 mu m for 1h) resulted in a significant increase in resistance (p=0.2, 0.01 and < 0.001 respectively). For pretreatment of SCC-25 cells with similar lowdoses of gamma-rays 10min before the challenge cisplatin dose, the increased resistance was reduced or absent and was only significantly increased for pretreatment with 25cGy and a challenge cisplatin dose of 0.1 mu m for 1h (p=0.02). Similar acute low-doses of gamma-rays given either 10 or 60min after the challenge cisplatin dose did not increase resistance. Conclusions: The human squamous carcinoma cell line SCC-25 showed a low-dose hypersensitivity to cisplatin followed by increased resistance at higher doses. Treatment of SCC-25 cells with low-doses of gamma-rays can induce a protective effect to a subsequent low-dose cisplatin challenge.