Development of a cancer DNA phenotype prior to tumor formation

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.3-methylcholanthrene ͉ antineoplastic agents ͉ cyclophosphamide ͉ cancer inhibition ͉ cancer prediction

A cancer DNA phenotype in healthy prostates, conserved in tumors and adjacent normal cells, implies a relationship to carcinogenesis

“…This phenotype was identified in normal tissues 8 weeks before tumor formation. Strikingly, administration of the prodrug cyclophosphamide every 10 days after 3-methylcholanthrene injection delayed tumor formation by about 30% and almost completely suppressed development of the phenotype, thus suggesting that it may also be inhibited by other intervention strategies with less toxic side effects (4).…”

“…tical models (1)(2)(3)(4)(5), we have demonstrated previously a cancer DNA phenotype in the limbs of mice 10 weeks after injecting the carcinogen 3-methylcholanthrene (4). This phenotype was identified in normal tissues 8 weeks before tumor formation.…”

Oxidative Changes in the DNA of Stroma and Epithelium from the Female Breast: Potential Implications for Breast Cancer

“…The DNA samples were also grouped by lesion concentrations, which revealed an uneven distribution of age relative to increasing values. In addition, we used Fourier transform-infrared (FT-IR) spectroscopy 5,[20][21][22] to delineate structural differences in the stromal DNA in relation to the various age groups and to determine whether such differences exist between the matched cell types.…”

Discrimination between healthy and tumor tissues on formalin-fixed paraffin-embedded breast cancer samples using IR imaging

“…Meanwhile, Mourant et al demonstrated that the ratio RNA/lipid could be used to determine the proliferative status of mammalian cells [13]. A diagnostic advantage of the FT-IR spectroscopy in cancer research is that the development of a cancer DNA phenotype can be observed prior to the tumor formation, notably for prostate carcinomas [11]. As tumorigenesis in humans is a multistep process, cells acquire several capabilities leading to the progressive conversion of normal human cells into cancer cells, notably the limitless potential of growth [8].…”