Bioactivation of polycyclic aromatic hydrocarbon carcinogens within the vascular wall: implications for human atherogenesis.
Atherogenesis is a complex pathogenetic process involving a variety of structural and functional deficits within the arterial wall that culminate in the formation of fibrous atherosclerotic plaques. Cigarette smoking is potentially the most remediable contributor to cardiovascular mortality and morbidity. Among the 4000 plus chemicals present in tobacco and tobacco smoke, polycyclic aromatic hydrocarbons (PAHs) have been firmly implicated in the etiology of atherosclerosis in experimental model systems. However, the molecular mechanisms responsible for PAH-induced vascular injury are not well understood. In this review, we have focused on the mechanisms of bioactivation of PAHs in the vas-culature, and the possible role(s) of cytochrome P4501A and 1B enzymes in the formation of PAH-DNA adducts within the vessel wall, a phenomenon that may contribute to the development of atherosclerotic plaques in humans.
Ramos
Kenneth S
KS
Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, Kentucky, USA.
Moorthy
Bhagavatula
B
D000818:Animals; D050197:Atherosclerosis / Q000139:chemically induced* / Q000201:enzymology / Q000378:metabolism; D001711:Biotransformation; D001808:Blood Vessels / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002273:Carcinogens / Q000493:pharmacokinetics* / Q000633:toxicity; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D018736:DNA Adducts / Q000378:metabolism*; D006801:Humans; D011084:Polycyclic Aromatic Hydrocarbons / Q000493:pharmacokinetics* / Q000633:toxicity
D002273:Carcinogens; D018736:DNA Adducts; D011084:Polycyclic Aromatic Hydrocarbons; D003577:Cytochrome P-450 Enzyme System