Effect of Essential Fatty Acid Deficiency on Ultrastructure and Growth of Transplantable Mouse Hepatoma BRL2

Abstract

Mouse hepatoma BRL was serially transplanted for 8 generations in hosts previously made deficient in essential fatty acids (EFA), and its ultrastructure and growth were compared with those of a subline of the same tumor in hosts on a control diet, and with the host's liver cells. The mitochondria of the hepatoma became progressively enlarged and pleomorphic. EFA-deficient liver mitochondria also enlarged, but were only rarely pleomorphic. Cristae mitochondriales in all hepatoma cells became vesiculative, suggestive of alteration in the membranes and accumulation of fluid between the inner and outer membranes. This appeared in the first transplant generation and persisted without change in all subsequent generations in EFA-deficient hosts. This was in contrast to the cristae of EFA-deficient hosts' livers which remained normal in appearance except that cristae in the periportal cells increased in length and number. After 8 transplant generations in EFA-deficient hosts, the hepatoma was serially transplanted for 4 generations in normal hosts. Vesiculation of mitochondrial cristae disappeared in the first generation. The increased size and pleomorphism persisted through the 4 generations, whereas mitochondria of EFA-deficient liver returned to normal size and ultrastructure within 10 days after the mice were restored to a control diet. EFA deficiency resulted in reduction in mitotic activity and growth rate of the tumor, but this was not progressive with successive transplantations. It has been tentatively concluded that the differences in reaction of the mitochondria of liver and hepatoma to EFA deficiency may be associated with repeated mitosis in the hepatoma.