Chromosome Fragments have the Potential to Predict Hyperthermia-induced Radio-sensitization in Two Different Human Tumor Cell Lines

Abstract

Cellular radiosensitivity, assessed by loss of clonogenicity, has been shown to correlate with the number of radiation-induced chromosomal aberrations. Also an increased radiosensitivity by hyperthermia has been shown to correlate with an increase in chromosomal aberrations. Therefore, determination of the number of chromosomal aberrations might be used as an assay to predict the radiosensitivity of tumors pre-treated with hyperthermia at clinically relevant temperatures. The use of premature chromosome condensation combined with fluorescent in situ hybridisation (PCC-FISH) has been shown to be clinically applicable. Therefore, the use of chromosomal aberrations as determined with PCC-FISH for the prediction of hyperthermia-induced radio-sensitization in human tumor cells was investigated. Confluent cultures of SW-1573 (human lung carcinoma) and RKO (human colorectal carcinoma) cells were treated with 1 h 41 degrees C or 43 degrees C hyperthermia prior to gamma-irradiation. Clonogenic cell survival and induction of chromosomal aberrations (unrejoined chromosomal fragments and translocations), by PCC-FISH, were studied at 24 h after treatment. Pre-treatment with hyperthermia at 41 degrees C for 1 h enhanced the radiosensitivity of RKO cells but not of SW-1573 cells. Increasing the temperature to 43 degrees C for 1 h enhanced the radiosensitivity of SW-1573 cells. When radio-sensitization was observed, a significant increase in the number of unrejoined chromosomal fragments was found but the frequency of translocations was not increased. Hyperthermia-induced radio-sensitization is correlated with an increase in unrejoined chromosomal fragments. This suggests that determination of the number of chromosomal fragments after hyperthermia and radiation treatment might be used for the prediction of combined treatment response in cancer patients.

Cell survival and radiosensitisation: Modulation of the linear and quadratic parameters of the LQ model

“…(40-42˚C) to increase radiosensitivity of human tumour cells has been shown to be cell line-dependent (8,26,(100)(101)(102)(103)(104)(105). In a study by Xu et al, pre-treatment of cells at 41.1˚C for 1 h did not induce radiosensitisation, whereas treatment for 2 h or more resulted in radiosensitisation in the HT-resistant but not in the HT-sensitive cell line (106).…”

“…A role for mitotic catastrophe, occurring as a result of G2/M checkpoint abrogation, has also been suggested (112). It has been demonstrated that radiosensitisation by HT at 41-43˚C correlates with an increased number of chromosomal fragments, but not of colour junctions, 24 h after treatment, compared to radiation alone (101). HT at clinically reachable temperatures mainly enhances the quadratic parameter, β, which represents the frequency of induction-repairable SLD.…”

Radiosensitization with Hyperthermia and Chemotherapeutic Agents: Effects on Linear-Quadratic Parameters of Radiation Cell Survival Curves

“…A role for mitotic catastrophe occurring as a result of G2/M checkpoint abrogation has also been suggested (Mackey & Ianzini, 2000). It has been shown that radiosensitization by 41-43C hyperthermia correlates with an increased number of chromosomal fragments, but not of color junctions, at 24h after treatment compared to radiation alone (Bergs et al, 2008).…”

Comparison of RBE values of high- LET α-particles for the induction of DNA-DSBs, chromosome aberrations and cell reproductive death

“…For induction of PCCs, 80 nM of Calyculin A was added for 1 h immediately after irradiation [2,5,38]. Visualization of chromosomes was accomplished by fluorescent in situ hybridization (FISH).…”