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.