Carcinogens Protein binding

N. and Pelkonen, 0. Oxidative metabolism of carcinogens by trout liver resulting in protein binding and mutagenicity. 

The carcinogenicity of af la toxin is reduced by protein deficiency, presumably because of reduced metabolic activation to the epoxide intermediate, which may be the ultimate carcinogen, which binds to DNA (Fig. 5.14). A deficiency in dietary fatty acids also decreases the activity of the microsomal enzymes. Thus, ethylmorphine, hexobarbital, and aniline metabolism are decreased, possibly because lipid is required for cytochromes P-450. Thus, a deficiency of essential fatty acids leads to a decline in both cytochromes P-450 levels and activity in vivo. 

Mechanistic assays Various systems, e.g. cell lines, cell-free extracts, mitochondria, nuclear extracts GAP junction inhibition, oxidative stress measure, protein-binding activity, endocrine-disrupting activity, oxygen consumption, metabolite levels, etc. Mechanistic studies Non-genotoxic carcinogenicity, weight of evidence... 

Covalent binding of chemical carcinogens to cellular macromolecules, DNA, RNA and protein, is wel1-accepted to be the first step in the tumor initiation process ( 1, 2). Most carcinogens, including polycyclic aromatic hydrocarbons (PAH), require metabolic activation to produce the ultimate electrophilic species which react with cellular macromolecules. Understanding the mechanisms of activation and the enzymes which catalyze them is critical to elucidating the tumor initiation process. 

Litwack G, Ketterer B, Arias IM (1971) Ligandin a hepatic protein which binds steroids, bilirubin, carcinogens and a number of exogenous organic anions. Nature 234 466 167 Lubchenco J, Gaines SD (1981) A unified approach to marine plant-herbivore interactions. 

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