Isolation and Characterization of Highly Radioresistant Malignant Hamster Fibroblasts that Survive Acute γ Irradiation with 20 Gy

Abstract

To study the acquired radioresistance of tumor cells, a model system of two cell lines, Djungarian hamster fibroblasts (DH-TK-) and their radioresistant progeny, was established. The progeny of irradiated cells were isolated by treating the parental cell monolayer with a single dose of 20 Gy (PIC-20). The genetic and morphological features, clonogenic ability, radiosensitivity, cell growth kinetics, ability to grow in methylcellulose, and tumorigenicity of these cell lines were compared. The plating efficiency of PIC-20 cells exceeded that of DH-TK- cells. The progeny of irradiated cells were more radioresistant than parental cells. The average D0 for PIC-20 cells was 7.4 +/- 0.2 Gy, which is three times higher than that for parental cells (2.5 +/- 0.1 Gy). Progeny cell survival in methylcellulose after irradiation with a dose of 10 Gy was 15 times higher than that of DH-TK- cells. In contrast to parental cells, the progeny of irradiated cells showed fast and effective repopulation after irradiation with doses of 12.5 and 15 Gy. The tumor formation ability of irradiated progeny cells was higher than that of parental cells; after 15 Gy irradiation, PIC-20 cells produced tumors as large as unirradiated progeny of irradiated cells, whereas the tumor development of DH-TK- cells diminished by 70%. High radioresistance of progeny of irradiated cells was reproduced during the long period of cultivation (more than 80 passages). The stability of the radioresistant phenotype of PIC-20 cells allows us to investigate the possible mechanisms of acquired tumor radioresistance.

Time-course analysis of DNA damage response-related genes afterin vitroradiation in H460 and H1229 lung cancer cell lines

“…Although H1299 is relatively radiosensitive, some cells ultimately survived and made visible colonies in the clonogenic assay (Figure 1). Many previous studies have reported that radioresistant subclones could be artificially derived from radiosensitive cancer cells (Tyrsina et al, 2005;Ogawa et al, 2006;Nojiri et al, 2009). According to our observation, it is likely that most of the genes in group A was associated with the initial step of signal transduction, which contributed as signal sensors and transducers (ATM, ATR, MRE11, 53BP1, TopBP1, Claspin and Chk2).…”

Radioresistance of Stat1 over-expressing tumour cells is associated with suppressed apoptotic response to cytotoxic agents and increased IL6-IL8 signalling

“…Tumour cells may acquire radioresistance using multiple pathways including those which are induced/altered by ionising radiation (IR) itself ( Lee and Bernstein 1993 , Tyrsina et al 2005 , Otero et al 2006 ). To investigate IR-induced tumour radio-resistance, a radiosensitive human squamous cell carcinoma tumour, SCC61, was passed and irradiated in vivo.…”

Contribution of Neuropilin-1 in Radiation-Survived Subclones of NSCLC Cell Line H1299

“…In radiotherapy, suppressing the occurrence of radioresistant tumor cells and tumor repopulation are severe issues for tumor control [7], and studies to understand the cellular characteristics of repopulated tumors using model-cells have been vigorously performed recently [19][20][21][22][23]. These model-cells that survived irradiation commonly show increased malignancy with increased invasiveness, adhesion, and motility, as in clinical cases.…”