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.