SIALIC ACID AND TUMORIGENESIS: A CANCER DETECTION POTENTIAL
Abstract
A priority objective of the National Cancer Program is the requirement for biochemical and/or immunological methods for the early detection of cancer based on analysis of exfoliated cells or body fluids obtained from apparently normal individuals. To investigate the association between sialic acid and tumorigenesis, transplantable hepatomas and squamous cell carcinomas were initiated with the carcinogen N-2-fluorenylacetamide and propagated in vivo and in tissue culture. Tumor lines varied in histological classification, growth rate, and ability to form pulmonary metastases. There was no correlation between growth rate and histological classification or between either of these two parameters and the ability to metastasize. Elevations of total and ganglioside sialic acid were noted in carcinogen-treated liver and in transplantable hepatoma tissue when contrasted with values from normal liver. Levels of sialic acid showed positive correlation with hepatoma growth rate. Ganglioside patterns from non-metastatic hepatoma lines showed a loss of G(,M3) and an increase in the ratio of the total monosialogangliosides to the disialiogangliosides. Metastatic lines contained more normal ganglioside patterns. Concomitant elevations of total and ganglioside sialic acid were observed in the serum of animals bearing subcutaneous implants. Serum levels of total sialic acid showed a positive correlation with tissue levels, but no correlation was observed between ganglioside and total serum sialic acid levels. Interest in the diagnostic possibilities of these observations prompted the development of a rapid technique for the estimation of ganglioside content in serum. The procedure, designated the citrate procedure, involved a chloroform-methanol extraction, precipitation of glyco- and lipoproteins with tripotassium citrate, and estimation of sialic acid by the thiobarbituric acid procedure. The lipid-associated sialic acid (LASA) values obtained with the citrate procedure estimated both ganglioside and lipid-soluble protein sialic acid content. LASA levels showed position correlation with extracted protein and with serum ganglioside levels. Elevations of LASA were observed in the sera of the following: mice bearing transplantable mammary carcinomas; rats bearing transplantable hepatomas; client-owned dogs and horses bearing a variety of tumors; and in the sera of humans bearing breast, colonic, and lung carcinomas. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of school.) UMI
Degree
Ph.D.
Subject Area
Biology
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