Effects of Pollutants on Vertebrate Cells in Vitro.
Final scientific rept. 1 Nov 79-31 Oct 82,
CALIFORNIA UNIV IRVINE DEPT OF DEVELOPMENTAL AND CELL BIOLOGY
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This study has investigated the effects of hydrazine Hz and monomethyl hydrazine MMH on several different cellular systems in vitro. The major cellular systems studied were cultured fibroblasts, epithelial cells, and rat myocardial cells. Both Hz and MMH had a toxic effect and inhibited cell growth in the concentration range of 0.1 mM - 10 mM. However, of greater significance was the finding that two major cellular target sites of Hz and MMH are the cell membrane and the mitochondria. These studies resulted in the development of a sophisticated laser based fluorescence stimulation and detection system that could be used as a sensitive assay tool for analyzing the cellular effects of many toxic agents. In addition to the outer membrane being affected by MMH it was demonstrated that ultrastructural alteration in mitochondria occurred. These structural effects correlated with cell surface electrical changes as evidenced by electrophysiological implantation of microelectrodes. Based upon the electrical and electron microscopic observations an alteration of calcium ion flux was hypothesized. In summary, this three year study has demonstrated that the toxicity of hydrazines may be based upon cell membrane and metabolic via mitochondrial effects alterations.