Chemoprevention of Rat Liver Carcinogenesis by S-Adenosyl-L-Methionine: Is DNA Methylation Involved?
Istituto di Patologia Generale dell'Università di Sassari, Italy.Basic life sciences 02/1993; 61:219-37. DOI: 10.1007/978-1-4615-2984-2_20
The best approach to the control of cancer incidence in a population at risk is the removal of the causative agent (primary prevention). However, when primary prevention cannot be applied, the occurrence of cancer can be prevented by administration, to populations at risk, of one or more chemical compounds (chemoprevention; Ref. 1–3). These compounds could interfere with cancer initiation by preventing the formation of ultimate carcinogens and carcinogen-DNA adducts, or by preventing carcinogens from reaching or reacting with critical targets. Once initiation occurs, chemopreventive agents may be used to kill preneoplastic cells or suppress their evolution to neoplastic cells. This latter goal could be reached by inducing preneoplastic cells to differentiate so that they remain viable but irreversibly lose their proliferative potential.
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ABSTRACT: The authors review ten essential amino acids with regard to their metabolic, physiologic and therapeutic effects throughout the human body. Physical properties of these biologically active compounds are discussed as a foundation for their diverse roles in special nitrogen containing products, neurotransmitters, and as alternative energy sources. Both normal and abnormal amino acid metabolism are considered in the areas of digestion, elimination of metabolic products, metabolic intermediates, and defects in these systems. Recent developments in therapeutic applications are further examined for clinical utility and as an economical alternative to traditional clinical treatment modalities.
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ABSTRACT: Inorganic arsenic (As), 1,2-dichloroethane (DCE), vinyl chloride (VC) and trichloroethylene (TCE) are frequently identified as groundwater contaminants near hazardous waste disposal sites. While the carcinogenicity of each of these chemicals has been extensively studied individually, little information exists regarding their carcinogenic potential in combination. Therefore, we investigated the carcinogenic promoting potential of chemical mixtures containing arsenic, DCE, VC and TCE following multiple initiator administration in a multiple organ carcinogenicity bioassay (N. Ito, T. Shirai, S. Fukushima, Medium-term bioassay for carcinogens using multiorgan models, in: N. Ito, H. Sugano (Eds.), Modification of Tumor Development in Rodents, Prog. Exp. Tumor Res., 33, 41-57, Basel, Karger, 1991). Our results reveal a dose-responsive antagonistic effect of this four-chemical mixture on the development of preneoplastic hepatic lesions (altered hepatocellular foci and glutathione S-transferase pi positive foci) as well as bronchioalveolar hyperplasia and adenoma formation.
Article: Alcohol and Liver Cancer[Show abstract] [Hide abstract]
ABSTRACT: Hepatocellular carcinoma is the eighth most frequent cancer in the world, accounting for approximately 500,000 deaths per year. Unlike many malignancies, hepatocellular carcinoma occurs predominantly within the context of known risk factors, with hepatic cirrhosis being the most common precursor to the development of hepatocellular carcinoma. After ethanol ingestion, the liver represents the major site of metabolism. Ethanol metabolism by alcohol dehydrogenase leads to the generation of acetaldehyde and free radicals that bind rapidly to numerous cellular targets, including components of cell signaling pathways and DNA. In addition to direct DNA damage, acetaldehyde depletes glutathione, an antioxidant involved in detoxification. Chronic ethanol abuse leads to induction of hepatocyte microsomal cytochrome P450 2E1, an enzyme that metabolizes ethanol to acetaldehyde and, in doing so, causes further free radical production and aberrant cell function. Cytochrome P450 2E1-dependent ethanol metabolism is also associated with activation of procarcinogens, changes in cell cycle, nutritional deficiencies, and altered immune system responses. The identification of oxidative stress in mediating many deleterious effects of ethanol in the liver has led to renewed interest in the use of dietary antioxidants as therapeutic agents. Included in this group are S-adenosyl-L-methionine and plant-derived flavanoids.
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