Lipophiles carcinogenicity

H. P. Shu and A. V. Nichols, Uptake of lipophilic carcinogens by plasma lipoproteins. Structure activity studies, Biochim. Biophys. Acta 665 376-384 (1981). 

RH above can represent a very wide variety of xenobi-otics, including drugs, carcinogens, pesticides, petroleum products, and pollutants (such as a mixture of PCBs). In addition, endogenous compounds, such as certain steroids, eicosanoids, fatty acids, and retinoids, are also substrates. The substrates are generally lipophilic and are rendered more hydrophilic by hydroxy-lation. 

In mammals the cytochrome P-U50 mediated monooxygenase or mixed function oxidase system involved in the elimination of lipophilic environmental contaminants and other foreign compounds, has been implicated in the carcinogen activation process. There are several distinct variants of cytochrome P-U50 in mammalian tissues and there may be more than one form of this ubiquitous cytochrome also in fish. The significance of this lies in the fact that different forms of cytochrome P-U50 result in different metabolite patterns, which in turn may reflect on the carcinogenicity or toxicity of compounds being metabolized. 

Amino groups Decreased lipophilic character Increased water solubility due to salt formation. Decreased lipid solubility. Provides a new centre for hydrogen bonding, which could influence the binding of the drug to the target site. The incorporation of aromatic amines is avoided as they are often toxic and/or carcinogenic. 

Singer, G.M., Taylor, H.W., Lijinsky, W. (1977) Lipophilicity as an aspect of nitrosamine carcinogenicity quantitative correlations and qualitative observation, Chem.-Biol. Interact. 19, 133-142. 

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