COMODULATION OF CELLULAR POLYAMINES AND PROLIFERATION - BIOMARKER APPLICATION TO COLORECTAL MUCOSA

Polyamines are low molecular weight aliphatic amines required for norm al cellular growth which are ubiquitously found in all living tissues. Polyamine biosynthesis is known to increase with mitogenesis, and ele vated polyamine concentrations are found in hyperproliferative tissues . Quantitation of tissue polyamine content may thus provide a biochemi cal measure of proliferation, with potential biomarker application to the colonic mucosa where dysregulated epithelial proliferation is asso ciated with cancer risk. This study was performed to validate polyamin e analyses as a measure of cellular proliferation, and to preliminaril y assess polyamine assay characteristics when applied to clinical samp les. Using FHC, a human colonic epithelial cell line, for in vitro exp erimentation, deoxycholic acid or retinol was added to freshly passage d cultures to either stimulate or inhibit proliferation, respectively. Parallel cultures were then assayed for (1) proliferation by sulforho damine B staining; and (2) polyamine content by a high-performance liq uid chromatographic method. Deoxycholic acid stimulated, and retinol i nhibited proliferation in dose-dependent fashion. Polyamine content, s pecifically the spermidine content and the spermidine/spermine ratio, also increased or decreased in response to culture with deoxycholic ac id or retinol, respectively. Significant linear correlations between p roliferation and spermidine (r = 0.858, P < 0.001), and with the sperm idine/spermine ratio (r = 0.574, P < 0.05) were observed. When quantit ative polyamine analyses were applied to human colonic specimens, repl icate mucosal sampling revealed a high degree of intra-individual vari ability, indicating a heterogeneous distribution of polyamines within anatomically confined colonic segments. The results support a role for quantitative polyamine analyses as a correlative measure of colonic e pithelial proliferation; however, intraindividual variability may limi t the utility of colorectal biomarker measurements. (C) 1995 Wiley-Lis s, Inc.