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Published on: July 25, 2017
Development of a cancer DNA phenotype prior to tumor formation
Donald C Malins1, Katie M Anderson, Naomi K Gilman
1Biochemical Oncology Program, Pacific Northwest Research Institute, 720 Broadway, Seattle, WA 98122, USA. dmalins@pnri.org
Abstract:
Using the carcinogen 3-methylcholanthrene (MCA), we demonstrate with Fourier transform-infrared spectroscopy that a cancer DNA phenotype is produced well in advance of palpable tumors. We further demonstrate that the administration of cyclophosphamide markedly inhibits the development of the cancer phenotype and concomitantly delays tumor formation. MCA, injected into the hind legs of mice, produced a variety of significant structural changes in the nucleotide bases and phosphodiester-deoxyribose backbone, as reflected in a substantial (34%) difference between the mean DNA spectra of the control and the MCA-injected mice. Strikingly, 57 days before the mean appearance of tumors, we could not distinguish the DNA structure of the histologically normal tissues of the MCA-injected mice from the DNA structure of the tumor tissues. This finding indicates the early development of a cancer phenotype. Confirmatory evidence was obtained when tissues from a group of mice injected with both MCA and cyclophosphamide did not manifest the cancer phenotype, and their mean DNA structure closely resembled that of the control mice. Accordingly, we propose that the cancer DNA phenotype, as evinced by Fourier transform-infrared spectroscopy, is a promising early indicator of tumor formation, and we postulate that agents capable of inhibiting this phenotype may delay or prevent carcinogenesis.
Insights
Fourier transform-infrared spectroscopy revealed a cancer DNA phenotype preceding tumors in mice treated with 3-methylcholanthrene (MCA). Cyclophosphamide inhibited this phenotype, delaying tumor formation, suggesting a promising early cancer detection method.
Area of Science:
- Molecular Biology
- Biochemistry
- Cancer Research
Background:
- Carcinogen exposure can induce DNA alterations.
- Early detection of cancer phenotypes is crucial for effective intervention.
- Fourier transform-infrared spectroscopy (FTIR) offers a method for analyzing molecular structures.
Purpose of the Study:
- To investigate the development of a cancer DNA phenotype using FTIR.
- To assess the effect of cyclophosphamide on the cancer DNA phenotype and tumor formation.
- To establish FTIR-detected DNA changes as an early indicator of carcinogenesis.
Main Methods:
- Mice were injected with the carcinogen 3-methylcholanthrene (MCA).
- DNA structural changes were analyzed using Fourier transform-infrared spectroscopy (FTIR).
- The impact of cyclophosphamide co-administration on DNA phenotype and tumor development was evaluated.
Main Results:
- MCA induced significant structural changes in DNA, evident as a 34% spectral difference between control and treated mice.
- A distinct cancer DNA phenotype was detected 57 days before tumor appearance, even in histologically normal tissues.
- Cyclophosphamide treatment inhibited the cancer DNA phenotype and delayed tumor formation.
Conclusions:
- A cancer DNA phenotype, detectable by FTIR, emerges early in carcinogenesis.
- FTIR analysis of DNA structure shows promise as an early diagnostic marker for tumor formation.
- Inhibiting the cancer DNA phenotype may represent a strategy to delay or prevent cancer development.
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