RETINOIC ACID AS A MITOTIC AND IONIC CONSTITUTIONAL STABILIZER IN AN ANEUPLOID HUMAN BREAST-CANCER CELL-LINE

The aneuploid human breast cancer cell line MDA-231 has been reported by us in a previous paper to increase intraclonal tumor genetic hetero geneity by a mitotic error in the distribution of protein (mass) and D NA to daughter cells. In the present investigation 13-cis-retinoic aci d (RA) was found to reduce tumor cell heterogeneity and to stabilize m itosis, resulting in a more even partition of mass and DNA without red ucing growth rate. X-ray microanalytical measurements of inorganic cat ions were made in the electron microscope, revealing a quite relevant decreased variation in all microanalytical measurements made after RA treatment. Depressed intracellular cytoplasmic sodium and chlorine lev els and unchanged potassium were found, as well as increased intracell ular sulphur. There was no change in overall protein content, nor any reproducible change in polypeptide 2-D gel electrophoretic pattern as a result of RA treatment. No evidence of reduced malignancy potential was found. In contrast, butyric acid was shown to both retard the grow th of exponentially growing MDA-231 cells and alter the polypeptide pa ttern, However, no evidence of reduced tumor cell heterogeneity was fo und following treatment with butyric acid. Our results indicate a stab ilizing effect of RA treatment, probably exerting its effect upon plas ma membranes and the mitotic spindle.