Ribonucleases and neoplasia.
Biochemical data provide good evidence of a lack of acid and alkaline RNase activities in ascites tumour cells. Analyses of whole solid tumours appear of doubtful value, but fractionation studies reveal RNase deficiencies in mitochondrial fractions whereas inconsistent results are reported for microsomal fractions. Nuclei, nucleoli, and ribosomes isolated from tumours show relatively weak activities. Large variations are noted in determinations on purified lysosomes. Histochemical analyses by two different approaches demonstrate a multifocal loss of RNase activities in preneoplastic tissues, a lack of activities in cancer cells, and the presence of appreciable activities in stromal tissue and necrotic areas of tumours. These results suggest that RNase activities found in homogenates and cellular fractions of heterogeneous tumours may derive mainly from stromal cells, phagocytes, and extracellular fluids of necrotic areas. A close correlation seems to exist between activation of RNases and tumour regression. A large variety of therapeutic agents induce increases in tumour RNase activities whereas ineffective agents do not. The activation of RNases precedes obvious regression and apparently represents de novo synthesis of RNases in cancer cells. It emerges from these studies that loss of RNase activities could represent a critical event in carcinogenesis, that RNase deficiencies would persist in cancer cells, and that RNase activation would be closely associated with tumour regression. Losses of RNase activities in preneoplastic tissues are followed by changes in the properties of cytoplasmic RNA probably due to alterations in ribosomes in areas of neoplastic transformation. Deficiencies in the RNase system could be the source of abnormalities in cellular RNA or RNA-containing particles that would lead to neoplasia.
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000473:pathology; D002455:Cell Division; D005455:Fluorescent Antibody Technique; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008861:Microsomes / Q000201:enzymology; D008928:Mitochondria / Q000201:enzymology; D009369:Neoplasms / Q000201:enzymology* / Q000503:physiopathology; D009374:Neoplasms, Experimental / Q000201:enzymology; D051381:Rats; D012260:Ribonucleases / Q000378:metabolism*
D012260:Ribonucleases