Biochemical and morphological changes induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in the rat liver cell plasma...

The administration of single oral doses of 200 micrograms kg-1 of 2,3,7,8-tetrachlorodibenzo-p-dioxin to females of the outbred, Lac : P strain of rat results in the formation of hepatic multinucleate cells by cell fusion. Liver cell plasma membranes isolated 6 or 11 days after dosing show two distinct changes. The first is a decrease of the activity of K+-Mg2+-ATPase, which confirms histochemical observations. The second is the formation, in those animals showing a more severe intoxication, of a population of plasma membranes which are less dense than usual and which consist of extended membrane sheets. It is suggested that these alterations are consequent on a disturbance of lipid metabolism in the hepatic cells and that they represent early manifestations of the toxic process which leads to the formation of multinucleate cells.