This biochemical research in one area of chemical carcinogenesis is aimed at furthering our understanding of (a) the detailed mechanisms that are involved in the metabolic activation of polycyclic hydrocarbons, (b) the reasons behind some of the striking structure: activity relationships that exist within this class of carcinogens and (c) the way in which hydrocarbons are activated by metabolism (i) in in vitro and in vivo studies using skin and keratinocytes from rodent species known to be either resistant or susceptible to hydrocarbon carcinogenesis and (ii) in in vitro studies using human skin and/or keratinocytes. The metabolism of a series of radioactively-labelled and structurally-realted hydrocarbons will be examined, and compared, using HPLC and a selection of reference compounds, and their activation to intermediates that react with nucleic acids will be studied in mouse skin and in hamster embryo cells using a combination of Sephadex LH20 column chromatography, HPLC and fluorescence spectrometry. The long term objectives of the work are (a) to enable us to predict the carcinogenicity of a polycyclic hydrocarbon from an examination of its structure and (b) to try to assess the susceptibility of human skin, in comparison with that of the skin of rodent species, to carcinogenesis by polycyclic hydrocarbons. A better understanding of the important factors and processes involved in polycyclic hydrocarbon carcinogenesis may eventually enable us to prevent some of the human cancer that is currently thought to be initiated by this class of chemical carcinogens.
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