Induction of Cytoplasmic Vacuolation by Two Alkyl-diamine Compounds

Abstract

Tetramethyl-1,4-butanediamine (TMBD) and tetramethyl-1,6-hexanediamine (TMHD) have been used as model compounds to study cytoplasmic vacuolation. These chemicals rapidly induced clear intracellular vacuoles in an intestinal cell line (I-407 human embryo-derived cells), in primary human smooth muscle cells and in Chinese hamster V79 cells. As has previously been reported, the induction of vacuolation was pH-dependent and dose-related. Vacuole formation was also found to be slowly reversible, and the degree of vacuole formation appeared to be determined not simply by the concentration of test material, but also by the amount of test material available per cell. V79 cells were markedly more sensitive to vacuole induction than the intestinal cells. Image analysis permitted the quantitation of vacuole induction. The vacuolation response is believed to result from lysosomal entrapment of the chemicals.