CORRELATION OF CELLULAR-DIFFERENTIATION IN HUMAN COLORECTAL-CARCINOMAAND ADENOMA CELL-LINES WITH METABOLITE PROFILES DETERMINED BY H-1 MAGNETIC-RESONANCE SPECTROSCOPY

The aim was to determine whether proton magnetic resonance spectroscop y (MRS) could grade human colorectal cells of differing malignant pote ntial. A cell model of tumour development and progression comprising 2 non-tumorigenic adenoma lines and 4 carcinoma lines of increasing tum origenicity was chosen. A gradual reduction in cellular differentiatio n and an accumulation of genetic alterations from adenoma to carcinoma characterized the selected cell lines. One-dimensional and 2-dimensio nal MRS showed that reduced differentiation in the cell model correlat ed with an increase in the levels of lipid, metabolites, the glycosyla tion intermediate uridine diphospho-N-acetylglucosamine and cell-surfa ce fucosylation. Mutations involving the K-ras, APC and DCC genes are present both in adenoma- and in carcinoma-derived lines in this model, but the first evidence of an abnormality in the p53 gene was concomit ant with the cells' ability to grow as a tumour in athymic nude mice. This genetic change coincided with the detection, by MRS, of UDP-hexos e (ribose moiety, 2D MRS cross peak between H2 at 4.38 ppm and H1 at 5 .99 ppm) and the appearance of an additional fucosyl resonance (cross peak between-CH3 at 1.41 and H5 at 4.30 ppm) in the least tumorigenic of the carcinoma cell lines. An increase in complexity of the fucosyla tion spectral pattern was observed with further cellular de-differenti ation and increased tumorigenicity. Collectively these data support th e existence of an adenoma-carcinoma sequence. (C) 1994 Wiley-Liss, Inc .