CANCER BIOMARKERS IN HUMAN ATHEROSCLEROTIC LESIONS - DETECTION OF DNA-ADDUCTS

Since somatic mutations are suspected to contribute to the pathogenesi s not only of cancer but also of atherosclerotic plaques, we measured DNA adducts in the smooth muscle layer of atherosclerotic lesions in a bdominal aorta specimens taken at surgery from seven patients. DNA add ucts were evaluated in three laboratories;by means of different molecu lar dosimetry methods, including: (a) HPLC/fluorescence, which specifi cally identifies the DNA adducts of the antibenzo(a)pyrene (BPDE) isom er; (b) two- and three-dimensional synchronous fluorescence spectropho tometries, which detect DNA adducts of BPDE and other reactive metabol ites of polycyclic aromatic hydrocarbons; and (c) P-32 postlabeling, w hich reveals the presence of a variety of types of DNA adducts. The HP LC/fluorescence method provided for the first time evidence for the pr esence of BPDE-DNA specific adducts in three of six specimens tested. Synchronous fluorescence spectrophotometry displayed broad areas of fl uorescence in all seven specimens, thereby suggesting the occurrence n ot only of BPDE-DNA but also of other DNA adducts with similar fluores cence characteristics. All specimens were also positive at P-32 postla beling, which revealed multiple spots detectable following enrichment either with nuclease P, or butanol, indicative of the presence of diff erent aromatic DNA adducts. Thus, the data obtained by applying typica l cancer biomarkers provide further support to the hypothesis that the re may be similarities between the carcinogenic and the atherogenic pr ocesses, and in particular that genetic alterations caused by DNA-bind ing agents in the artery wall may be detected in atherosclerotic lesio ns.