Conventional and fractionated 6 MV X-ray induced adaptive response in normal and transformed cell lines of head and neck and breast origin, and their relevance in cancer therapy.

PURPOSE: Cancer cells become resistant to radiation therapy (RT) due to radiation-induced adaptive response (RIAR). Studies emphasize the potential of hyper-fractionated RT in improving treatment outcomes for cancer patients, suggesting a paradigm shift to combat radio-resistance while minimizing adverse effects. Though the phenomenon of RIAR has been studied and reported from a radiation protection perspective, its role in clinical-RT remains unclear.

MATERIAL AND METHODS: The present study evaluated RIAR in tumor and normal cells of head and neck (squamous cell carcinoma-131 (SCC-131) and human gingival fibroblast (HGF)) and breast origin (MCF-7, MDA-MB-231, and MCF-10A) exposed in vitro to priming dose (PD) (0.25 Gy) and challenging (conventional (CCD): 2 Gy and fractionated (FCD): 1.2 + 1.2 Gy) doses of X-rays. DNA damage was measured using gamma H2AX (γ-H2AX) and micronucleus (MN) assays and cell survival using colony forming assay.

RESULTS: All cells showed attenuated DNA damage upon exposure to PD followed by CCD and FCD revealing the existence of RIAR. A decreased survival in SCC-131 and MCF-7 in FCD indicated the absence of RIAR; however, an increased cell survival in CCD suggests the existence of RIAR. In contrast, the MDA-MB-231 cell survival showed RIAR in FCD and no RIAR in CCD indicating the different response among cell types. Though DNA damage was observed, the survival of HGF and MCF-10A exposed to both CCD and FCD indicates the absence of RIAR.

CONCLUSIONS: Overall, the study suggests that compared to conventional regime, the fractionated regime serves to improve therapeutic efficacy by minimizing the damage to healthy cells while enhancing tumor cell killing.