Lipid composition, physical state, and lipid peroxidation of tumor membranes

Studies were carried out on microsomes isolated from the highly differentiated (slow-growing) Morris hepatoma 9618A, on microsomes and plasma membranes from the poorly differentiated (fast-growing) Morris hepatoma 3924A, and rat liver used as control. The lipid composition (phospholipid and cholesterol content, degree of fatty acid unsaturation) and peroxidation of such membranes has been correlated with the order and fluidity of the membrane bilayer. The results indicate that substrate availability is the rate-limiting step in microsomal and plasma membrane lipid peroxidation of hepatoma 3924A. From diphenylhexatriene fluorescence depolarization measurements it appears that the changes in lipid composition cause an increase in the order of the lipid bilayer on going from the control to hepatoma 9618A and 3924A microsomes, while fluidity is virtually unchanged. Conversely, for similar chemical changes, in plasma membranes from hepatoma 3924A the order is nearly the same and there is a decrease in fluidity. The changes in the above parameters of tumor membranes might be partly related to the loss of protective enzymes against oxygen radicals. This is supported by the observation that inhibition of liver superoxide dismutase and glutathione reductase, by treatment of rats with diethyldithiocarbamate and chloroethyl nitrosourea, respectively, renders the microsomal membranes more resistant to lipid peroxidation in vitro.