Interactions of Carcinogens with Nucleic Acids

Abstract

Since the discovery in the 1960s that chemical carcinogens can covalently react with nucleic acids, there have been a multitude of publications describing these interactions, identifying the chemical structures of the DNA adducts, studying their enzymic removal, the biological consequences and correlating extents of adduction with carcinogenic response. The majority of these studies have been centred on experimental models and only a few on man, in real carcinogen exposure situations. Up until recently we still did not have direct evidence that chemical carcinogens interact with human DNA in the target organ. This position has become clearer with the advent of various methods to measure carcinogen-DNA adducts in human tissues. Our laboratory has been particularly involved in developing immunological methods to both concentrate and quantify two potential human carcinogens, aflatoxin B₁ (AFB₁) and benzo(a)pyrene (BP). We have used immunoaffinity concentration prior to immunoassay of purified DNA and have found strong evidence that BP adducts are present in human lung tissue and AFB₁ adducts in human liver. Our most recent results indicate that combining immunological procedures with physicochemical methods, such as P³²-postlabelling, enables us to measure adduct concentrations as low as 1 adduct per 10¹⁰ bases. The implications of these findings will be discussed in relation to risk assessment.