Abstract
Carcinogenesis involves the chemical and structural alteration of biomolecules in cells. Aberrant methylation of DNA is a well-known carcinogenic mechanism and a common chemical modification of DNA. Terahertz waves can directly observe changes in DNA because the characteristic energies lie in the same frequency region. In addition, terahertz energy levels are not high enough to damage DNA by ionization. Here, we present terahertz molecular resonance fingerprints of DNA methylation in cancer DNA. Methylated cytidine, a nucleoside, has terahertz characteristic energies that give rise to the molecular resonance of methylation in DNA. Molecular resonance is monitored in aqueous solutions of genomic DNA from cancer cell lines using a terahertz time-domain spectroscopic technique. Resonance signals can be quantified to identify the types of cancer cells with a certain degree of DNA methylation. These measurements reveal the existence of molecular resonance fingerprints of cancer DNAs in the terahertz region, which can be utilized for the early diagnosis of cancer cells at the molecular level.
Highlights
We show the molecular resonance fingerprints of DNA methylation in the THz region and observe them in genomic DNA from cancer cells
THz waves are sensitive to chemical changes in molecules, and because DNA methylation is known to be among the major chemical factors influencing oncogenesis, we focus on the signals generated by these chemical changes using THz techniques
Because DNA methylation is not affected by nucleoside polymerization, we chose DNA methylation as a marker to follow the chemical changes in DNA induced by carcinogenesis
Summary
We show the molecular resonance fingerprints of DNA methylation in the THz region and observe them in genomic DNA from cancer cells. We quantify the degree of genomic DNA methylation based on THz absorption data and distinguish among several types of cancer cell lines using the quantified results. In cancer DNA, hypermethylation occurs at CGIs, and hypomethylation occurs in the repeated sequences[37,38] (Fig. 1a) This change can be measured at the whole-DNA level by comparing the methylation degree of cancer and normal DNA (Fig. 1b,c). These molecules have a few weak resonances that differ from the 5-mC peak positions at both room temperature and 85 K. This result indicates that the three major resonance peaks of 5-mC are THz fingerprints of nucleoside methylation
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