Non-thermal DNA damage of cancer cells using near-infrared irradiation.

We previously reported that near-infrared irradiation that simulates solar NIRnear-infrared irradiation with pre- and parallel-irradiational cooling can non-thermally induce cytocidal effects in cancer cells. To explore these effects, we assessed cell viability, DNA damage response pathways, and the percentage of mitotic cancer cells after near-infrared treatment with near-infrared irradiation. Further, we evaluated the anti-cancer effects of near-infrared irradiation compared to doxorubicin in xenografts in nude mice by measuring tumor volume and assessing protein phosphorylation by immunoblot analysis. The cell viability of A549 lung adenocarcinoma cells was significantly decreased after three rounds of near-infrared irradiation at 20 J ⁄cm(2) and drastically reduced after 4 and 5 rounds of near-infrared irradiation at that dose. The apoptotic cells were observed in near-infrared treated cells. Moreover, near-infrared irradiation increased the phosphorylation of ATM at Ser1981, H2AX at Ser139, CHK1Chk1 at Ser317, SMC1 at Ser966, and AKT at Ser473 in A549 cells compared to controls. Notably, near-infrared treatment induced nucleic foci formation of γH2AX. The percentage of mitotic A549 cells, as measured by histone H3 phosphorylation, significantly decreased after three rounds of near-infrared irradiation at 20 J ⁄cm(2) . Both near-infrared irradiation and doxorubicin inhibited the tumor growth of MDA-MB435 xenografts in nude mice and increased the phosphorylation of p53 at Ser15, CHK1Chk1 at Ser317, SMC1 at Ser966, and H2AX at Ser139 compared to control mice. The results of this study indicate that near-infrared irradiation can non-thermally induce cytocidal effects in cancer cells as a result of activation of the DNA damage response pathway. The near-infrared Near-infrared irradiation schedule used here reduces discomfort and side effects and can reach deep subcutaneous tissues, which facilitates safe repeated rounds of irradiation. Therefore, this strategy may have a potential application for treating cancer.
© 2012 Japanese Cancer Association.
PMID: 22515193