SEMINARS ON LIVER-DISEASE .13. HEPATIC ROLE IN CARCINOGENESIS AND ITS EARLY DETECTION - VINYL-CHLORIDE MODEL

  • 1 January 1978
    • journal article
    • research article
    • Vol. 51  (1) , 67-80
Abstract
The liver''s role in vinyl chloride toxicity and carcinogenicity is providing a better understanding of the chemical carcinogenesis mechanism. A variety of malignant and benign hepatic tumors was demonstrated with prolonged exposure to vinyl chloride. The multisystem involvement of this carcinogen and toxin provided a model for the study of chemical carcinogenesis common to man and animal. Clinical studies showed the usefulness of biochemical, radioisotopic and radiological studies in the detection of toxic and carcinogenic lesions. Animal studies demonstrated the biochemical metabolism by the liver of vinyl chloride-produced intermediates which are mutagenic in bacterial systems and may be the ultimate carcinogens. Hepatic subcellular enzyme studies prove preliminary evidence of cellular adaptation and increased detoxification. Disruption of this oxidization and detoxification balance may be the key to malignant transformation of cells. A working hypothesis is presented which may explain the metabolism of vinyl chloride into mutagenic intermediates by liver cells and the development of malignant transformation by extrahepatic sinusoidal lining cells, lung cells and brain tissue.