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12C-Beam Induces More Chromosomal Damage In Chemo-Radio-Resistant Cells Than 16O-Beam

Utpal Ghosh, Regina Lichti Binz, Ratan Sadhukhan, Asitikantha Sarma, Subrata Kumar Dey,Martin Hauer-Jensen, Rupak Pathak

The major challenge to eradicate cancer is the development of resistance to chemo- and/or radio-therapy. Recent studies indicate that particle radiation or high-LET (linear energy transfer) radiation kills cancer cells more effectively than low-LET gamma- or X-rays, potentially by inducing complex chromosomal aberrations (CAs). However, the efficacy of inducing chromosomal damage by various high-LET radiations has not been well-studied, specifically in cells resistant to both chemotherapeutic drug as well as ionizing radiation. To address the issue, we exposed a chemo-radio-resistant cell strain M5, which is derived from Chinese hamster lung fibroblast V79 cells, to ¹²C- and ¹⁶O-beams using a Pelletron accelerator. Aberration frequencies were scored at two different post-irradiation times (24 h and 48 h) using Giemsa staining technique. A linear dose-dependent increase in CAs was noticed at 24 h and 48 h after ¹²C-irradiation. Similar linear dose-response was also observed after ¹⁶O-irradiation at 24 h, but not at 48 h. In addition, difference in aberration spectrum was noticed based on radiation quality and post-irradiation incubation times. The dose-response curves revealed that ¹²C-beam induces more CAs than ¹⁶O-beam. This data clearly suggests that the extent and spectrum of chromosomal damage depends on the quality of high-LET radiation as well as the post-irradiation incubation time. These findings could potentially have applications in selecting beam parameters during hadron therapy (high-LET radiation therapy), particularly to eradicate chemo-radio-resistant tumors.