OXY-RADICAL METABOLISM AND CONTROL OF TUMOR-GROWTH

1. The content of oxy-radical scavenging enzymes is decreased in Morris hepatomas in a fashion which is inversely related with the growth rate of the tumour. 2. Hepatoma microsomal membranes are more resistant than normal rat liver membranes to lipid peroxidation induced in vitro by organic hydroperoxides or superoxide radicals. 3. In tumour membranes the most relevant rate-limiting factor of peroxidation is the low availability of polyunsaturated fatty acids (PUFA). Besides lipids, some proteins (particularly cytochrome P-450) act as controlling factors of peroxidation. 4. Tumour microsomes are more ordered and less fluid than liver microsomes. The latter, exposed to superoxide radical attack, exhibit chemical (fatty acid composition) and physical (molecular order) properties that are similar to those of transformed cell membranes. 5. These data indicate an aberration in the oxy-radical metabolism of cancer cells, and a sequence of events is hypothesized that could drive the transformed cell towards uncontrolled proliferation.