COMPARATIVE-STUDIES ON CYTOTOXICITY OF MICROPOLLUTANTS IN WATER - PRINCIPLE OF CYTOTOXICITY MATRIX

Cytotoxicities were investigated with chemicals including pesticides, industrial materials, and chlorination by-products using colony format ion inhibition of L-929 cells and membrane damage of ''liposomes'' to develop the simple bioassays for estimation of human hazardous micropo llutants in water. Some chemicals including pesticides and chlorinatio n by-products strongly inhibited colony formation of L-929 cells, and the inhibition was dose dependent. But most cytotoxic substances did n ot increase membrane permeability of liposomes, suggesting that cytoto xicity of these chemicals does not arise from direct damage of cell me mbranes. The IC10 and IC50, 10 and 50% inhibition concentrations, were obtained from the dose-response curve of colony formation. The IC10 s howed good correlation (r = 0.75) to LD50 of rat by intraperitoneal ad ministration but not to those by oral administration. The results were compared to those with viability of HL-60 cells, phagocytic activity of mice peritoneal macrophages, glycogenolysis, and LDH release of rat liver hepatocytes. The susceptibilities were largely different among these cytotoxicity tests, and the colony formation inhibition test gav e similar results to the viability of HL-60 cells. The principle of '' cytotoxicity matrix'' was developed from the comparison of cytotoxicit ies for each chemical. The characteristic relation was found between t he chemical structure and the pattern of the cytotoxicity matrix, indi cating that the cytotoxicity matrix may be useful for predicting the o rigin and nature of micropollutants. (C) 1994 by John Wiley & Sons, In c.