Abstract
DNA methylation is a pivotal epigenetic modification of DNA that regulates gene expression. Abnormal regulation of gene expression is closely related to carcinogenesis, which is why the assessment of DNA methylation is a key factor in cancer research. Terahertz radiation may play an important role in active demethylation for cancer therapy because the characteristic frequency of the methylated DNA exists in the terahertz region. Here, we present a novel technique for the detection and manipulation of DNA methylation using terahertz radiation in blood cancer cell lines. We observed the degree of DNA methylation in blood cancer at the characteristic resonance of approximately 1.7 THz using terahertz time-domain spectroscopy. The terahertz results were cross-checked with global DNA methylation quantification using an enzyme-linked immunosorbent assay. We also achieved the demethylation of cancer DNA using high-power terahertz radiation at the 1.7-THz resonance. The demethylation degrees ranged from 10% to 70%, depending on the type of cancer cell line. Our results show the detection of DNA methylation based on the terahertz molecular resonance and the manipulation of global DNA methylation using high-power terahertz radiation. Terahertz radiation may have potential applications as an epigenetic inhibitor in cancer treatment, by virtue of its ability to induce DNA demethylation, similarly to decitabine.
Highlights
Epigenetic modification is the heritable change without alterations in the DNA sequence
The amplitudes of the peaks range from 10 to 20 cm−1, depending on the type of cancer cell line. (d) Verification of the DNA methylation degree measured by THz time-domain spectroscopy (THz-TDS) by comparing the results with those obtained from the global DNA methylation quantification using the enzyme-linked immunosorbent assay (ELISA) method
The THz results mostly agree with the ELISA method, which implies that the global DNA methylation degree could be measured directly using the THz-TDS quantification technique
Summary
In order to successfully detect and manipulate DNA methylation, the resonance frequency of the methyl-DNA bond should be found first. The THz results showed mostly good agreement with the results obtained using the ELISA method, demonstrating that the THz-TDS technique can directly measure the global DNA methylation degree in blood cancer cell lines (Fig. 1d). If the degree of global methylation is reduced, the intensity of the resonance peaks observed using THz-TDS will be decreased after exposure to high-power THz radiation (Fig. 2e). The reduction ratios varied according to cell line (approximately 10–70%), the degree of methylation was substantially decreased in most of the samples (Fig. 4b, Table 1) These results may be a strong evidence that the demethylation of the blood cancer DNA occurs in the specific resonance frequency. Resonant high-power THz radiation significantly induces global demethylation in genomic blood cancer DNA, and the rate of reduction varies according to cell line
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