UVA light-induced DNA cleavage by selected polycyclic aromatic hydrocarbons.

Abstract

Polycyclic aromatic hydrocarbons (PAH) are ubiquitous environmental carcinogens (Connell et al. 1997; Conney, 1982; Dipple, 1985; Lesko, 1984). They are produced during forest fire, volcanic eruption, incomplete burning of fuel and other materials, tobacco smoke, and food processing (Baum, 1978; Connell et al. 1997). Exposure to PAHs has been linked to the development of skin and lung cancers as it is summarized in the 8th Report on Carcinogens (National Toxicology Program, 1998). PAHs are considered relatively nontoxic themselves, but they can be activated after entering the cell. The first activation pathway is metabolism. PAH metabolic products, diol-epoxides or diones, are known to be carcinogenic through DNA covalent product formation (Connell et al. 1997; Conney, 1982; Devanesan et al. 1996; Dipple, 1985; Lesko, 1984). The diol-epoxides can alkylate DNA, usually form a bond to the exocyclic amino group of the guanine residue in duplex DNA (Geacintov et al. 1997). The diones are able to oxidatively damage DNA by generation of free radicals, which either cause DNA damages or form DNA covalent products (Chen et al. 1996; Devanesan et al. 1996). Another pathway that enhances PAH toxicity is light activation. There have been studies on the photo-induced toxicity of PAH mixtures or individuals in the marine sediment toward micro-organisms and plants in the aquatic systems (Pelletier et al. 1997; Swartz et al. 1997). It is found that PAHs are generally more toxic when the system is exposed to the simulated solar radiation (ssr) than if it is kept in the dark. The increase in toxicity due to ssr can exceed 100 times (Swartz et al., 1997). It is suggested that PAHs act as photosensitizers (Pelletier et al. 1997). After absorbing UV light energy, PAHs in the excited-state may transfer its energy to molecular oxygen to produce reactive oxygen species that can cause a variety of damages to the cell. The phototoxicity can also be due to DNA covalent product formation from earlier studies. These works showed that, under light irradiation, benzo[a]pyrene can form DNA covalent adducts or cause DNA strand breakage (Blackburn et al. 1977; Brooks and Lawley, 1964; Hoard et al. 1981; Santamaria et al. 1966; Striste et al. 1980). The presence of benzo[a]pyrene can also increase the formation of 8-hydroxy-2′-deoxyguanine (Liu et al., 1998), a compound generated by oxidative damage of DNA. These DNA damage mechanisms have been suggested to relate to tumor induction and other adverse effects (Brooks and Lawley, 1964; Camalier et al. 1981; Santamaria et al. 1966). However, the studies so far have mostly focused on benzo[a]pyrene alone. In this research, we will examine light-induced DNA cleavage by the environmental contaminants: a series of 3, 4, 5-ring PAHs and their derivatives.