Pre-exposure of human squamous carcinoma cells to low-doses of gamma-rays leads to an increased resistance to subsequent low-dose cisplatin treatment
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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 microM for 1 h) and assayed for survival using a conventional colony assay. For SCC-25, various doses of gamma-rays (5 cGy to 2.5 Gy) were given either 10 or 60 min before the cisplatin challenge dose as well as either 10 or 60 min after the cisplatin challenge dose. RESULTS: Low-dose (0.5, 0.75 and 1 microM for 1 h) 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, 25 cGy or 1 Gy gamma-rays given 60 min before a low-dose cisplatin challenge (0.1 and 1 microM for 1 h) resulted in a significant increase in resistance (p=0.2, 0.01 and <0.001 respectively). For pretreatment of SCC-25 cells with similar low-doses of gamma-rays 10 min before the challenge cisplatin dose, the increased resistance was reduced or absent and was only significantly increased for pretreatment with 25 cGy and a challenge cisplatin dose of 0.1 microM for 1 h (p = 0.02). Similar acute low-doses of y-rays given either 10 or 60 min 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.
