Experiments were carried out to determine if the difference in rates of cell proliferation between normal and neoplastic cells may be related to altered levels of oxidative
enzymes. Assays were performed using homogenates from
hepatocellular carcinoma HC-252, a rapidly growing and moderately well-differentiated
tumor; from normal liver; and from the liver of the
tumor-bearing ACI rat. Results of the mitochondrial
enzymes indicated that the activities of
cytochrome oxidase and
succinate dehydrogenase were 3-fold lower in
tumor homogenates than in liver homogenates.
Monoamine oxidase activity could not be detected in HC-252; mixing experiments indicated no inhibitor was present in HC-252. Activities of th peroxisomal
enzymes,
urate oxidase,
D-amino acid oxidase, and
L-alpha-hydroxy acid oxidase were either undetected in the
tumor or were 12-fold lower than in liver homogenates. The activity of
xanthine oxidase, a cytoplasmic
enzyme, was 5- to 6-fold lower in the
tumor.
Catalase activity in the
tumor was also lower than in liver; this may be indicative of a lower oxidative environment at the cellular level. These
enzyme activities of the liver of
tumor-bearing rats were in the same range as those of normal rat liver, except that
D-amino acid oxidase activity was slightly lower, and
catalase activity was markedly lower and varied in a wide range. These results show an inverse correlation between the activities of
oxygen-utilizing
enzymes and rates of proliferation of one
tumor line and its control. The possible implications of these results in
neoplasia, cell proliferation, and cellular aging are discussed.