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Publication : Development of a cancer DNA phenotype prior to tumor formation.

First Author  Malins DC Year  2004
Journal  Proc Natl Acad Sci U S A Volume  101
Issue  29 Pages  10721-5
PubMed ID  15249662 Mgi Jnum  J:91488
Mgi Id  MGI:3047193 Doi  10.1073/pnas.0403888101
Citation  Malins DC, et al. (2004) Development of a cancer DNA phenotype prior to tumor formation. Proc Natl Acad Sci U S A 101(29):10721-5
abstractText  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.
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