Activities of nucleases (acid DNase and neutral RNase) known to be involved in carcinogenesis and suppression of cancer were determined in cancer tissue, serum and ascitic fluid of patients with hepatocellular carcinoma and were compared with those of the controls. Also studied were nucleases and nuclease-inhibitors isolated from hepatocellular carcinoma tissue and ascitic fluid of the cancer patients to evaluate the properties and interactions between them.
Activities of DNase, RNase and RNase inhibitor were significantly increased, suggesting the use of the nucleases and the inhibitor as biochemical markers for the hepatocellular carcinoma. DNase activity was not detected, RNase activity was increased and RNase inhibitor activity was unchanged in both serum and ascitic fluid of the hepatocellular carcinoma patients. The results indicated that RNase was released into the body fluid from the cancer tissue and that the RNase could be used as a diagnostic marker for the hepatocellular carcinoma.
DEAE-cellulose column chromatographical analyses revealed that DNase was isolated as a single enzyme and RNase as seven isozymes from the hepatocellular carcinoma tissue. The DNase isolated was preferentially cleaved ds DNA over ss DNA and was endonuclease in nature (majority of hydrolytic products of DNA by the DNase were oligodeoxyribonucleotides), suggesting an important role of the DNase in carcinogenesis of the liver. Of seven RNase isozymes isolated from the hepatocellular carcinoma tissue, isozyme I exhibited nonsecretory nature of RNase and other six isozymes secretory nature of the enzyme. Activity of RNase isozyme V was greatly increased and the activity of inhibitor complexed with the isozyme V was also increased in the cancer tissue.
RNase in ascitic fluid of the cancer patient was separated into four isozymes, of which isozyme I exhibited mixed form of secretory and nonseretory nature and greatly increased in its activity. RNase isozyme V isolated in the hepatocellular carcinoma tissue was not detected in the ascitic fuild. The results indicated that RNase isozyme V was limited in the cancer tissue and that RNase isozyme I and V and inhibitors associated with these isozymes might be involved in carcinogenesis processes, supression of cancer and maintenance of hepatocellular carcinoma through their interactions.
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