Bioactivation of Polycyclic Aromatic Hydrocarbon Carcinogens within the vascular Wall: Implications for Human Atherogenesis

Abstract

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.

Key Words :

• Atherogenesis
• Benzo(a)pyrene
• Polycyclic aromatic hydrocarbons
• 3-Methylcholanthrene
• DNA adducts
• Vascular smooth muscle cells
• ³²P-postlabeling
• Cytochrome P4501A1
• Cytochrome P4501B1