Cell Demeth lation using Resonant Terahert Radiation for Potential Cancer Treatment Joo-Hiuk Son1,2 and H a eong Cheon1 1
Uni e i of Seo l, Seoul 02504, Republic of Korea 2 iNe , Inc., G eonggi-do, Republic of Korea Email: joohi k@ o .ac.k from human embr onic kidne cell line (293T) as utili ed as a control and a part of it as artificiall meth lated to give M293T b DNA meth ltransferase en me (DNMT). The M293T as divided into t o and one of them as irradiated ith high-po er terahert radiation. The meth lation level of M293T as high but it as decreased to half close to the level of 293T after the e posure. To identif the effect in actual cancer DNA, e applied highpo er terahert radiation on some t pes of blood cancer DNA to assess the demeth lation. The blood cancer DNA e periment as performed in the same method ith the M-293T. The degree of DNA meth lation as significantl decreased in most of the blood cancer, although the demeth lation ratios varied according to cell line (appro imatel 10 - 70%) [5]. Also, the effective demeth lation of melanoma cells, ithout e tracting the cancer DNA, as achieved using a resonant terahert radiation [6].
Ab ac Carcinogenesis involves DNA methylation which is a primary alteration in DNA in the development of cancer before genetic mutation. Because the abnormal DNA methylation is found in most cancer cells, assessment of DNA methylation using terahertz radiation can be a novel optical method to detect and control cancer. The methylation has been directly observed by terahertz spectroscopy in the terahertz region and this epigenetic chemical change could be manipulated to the state of demethylation using resonant terahertz radiation. Demethylation of cancer cells is a key issue in epigenetic cancer therapy and our results may lead to the treatment of cancer using electromagnetic waves. I. INTRODUCTION ERAHERTZ electromagnetic aves, hose spectrum lies bet een micro ave and infrared regions (0.1-10 TH ), have been utili ed for the diagnosis and imaging of cancer [1-3]. In the effort of finding a specific signal in such measurements, a terahert resonance fingerprint of cancer has been directl observed at 1.6 TH for several t pes of cancer [4]. The resonant signal is believed to originate from the aberrant meth lation in DNA hich is an epigenetic modification before genetic mutation in the development of cancer. If it is a true resonant feature, this might be controlled or manipulated b using a terahert radiation at the frequenc . In the presentation, the details of finding the terahert resonance of cancer DNA coming from meth lation and the manipulation to demeth lation using resonant terahert radiation ill be e plained. Also, ho the demeth lation is related to cancer treatment ill be discussed.
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III. SUMMARY The result demonstrates that the molecular resonance of cancer DNA e ists in the terahert region and this can be controlled b the irradiation of high-po er terahert radiation. This is the first result using an optical technique for manipulating DNA meth lation. The manipulation of meth lation in cancer DNA is an important issue in epigenetic cancer therap because aberrant DNA meth lation can lead to abnormal gene e pression. Although there are several chemical inhibitor drugs for DNA demeth lation, hich reduce aberrant DNA meth lation in cancer cell, the still have a high risk of side effects. Because our method is a non-invasive, non-ioni ing and non-labelling technique, and uses specific resonance frequenc , it can be a great solution to achieve a novel cancer therap ith fe side effects. This implies that, like genetic scissors in biolog , terahert technique ma be applied as epigenetic scissors hich could lead to the demeth lation of cancer DNA.
II. RESULTS DNA meth lation pla s a role to regulate gene e pression. Because abnormal regulation of gene e pression can cause carcinogenesis, DNA meth lation is a critical factor in cancer research and treatment. In aqueous solutions, e tracked and observed the molecular resonance of genomic DNA at 1.6 TH from t o controls (293T, M-293T) and five cancer (PC3; prostate cancer, A431; skin cancer, A549; lung cancer, MCF-7; breast cancer, SNU-1; gastric cancer) cell lines, using free ing technique and baseline correction [4]. The resonance peak of spectrum presents the e istence and quantit of meth lation in DNA, but also the target for manipulation of DNA meth lation to control gene e pression in cancer DNA b breaking its bond. To break the meth lation resonantl , e irradiated a resonant high-po er terahert radiation, hich is generated from a LiNbO3 cr stal driven b 1-kH regenerative amplifier and has a limited band idth around the resonance frequenc of DNA meth lation b a bandpass filter, onto some t pes of cancer DNA. The DNA
REFERENCES [1] J.-H. Son, ed., Te ahe Biomedical Science and Technolog , 1st ed., Boca Raton, FL, USA: CRC, 2014. [2] J.-H. Son, e al., Potential clinical applications of terahert radiation, J. Appl. Ph ., vol. 125, 190901, 2019. [3] H. Cheon, e al., To ard clinical cancer imaging using terahert spectroscop , IEEE Sel. Top. Q an . Elec., vol. 23, 8600109, 2017. [4] H. Cheon, e al., Terahert molecular resonance of cancer DNA, Sci. Rep., vol. 6, Nov. 2016, Art. no. 37103. [5] H. Cheon, e al., Detection and manipulation of meth lation in blood cancer DNA using terahert radiation, Sci. Rep., vol. 9, Apr. 2019, Art. no. 6413. [6] H. Cheon, e al., Effective demeth lation of melanoma cells using terahert radiation, Biomed. Op . E p., vol. 10, 4931, Oct. 2019
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