Genotoxicity of Combined Exposure to Polycyclic Aromatic Hydrocarbons and UVA—A Mechanistic Study

Abstract

Solar UV radiation and benzo[a]pyrene (BaP) are two carcinogenic agents. When combined, their deleterious properties are synergistic. In order to get insights into the underlying processes, we carried out a mechanistic study within isolated DNA photosensitized to UVA radiation by either BaP, its diol epoxide metabolite (BPDE) or the tetraol arising from the hydrolysis of this last molecule. Measurement of the level of the oxidized base 8-oxo-7,8-dihydroguanine revealed that BaP is a poor sensitizer while BPDE and tetraol are more potent ones. None of these compounds was found to photosensitize formation of cyclobutane pyrimidine dimers through triplet energy transfer. On the basis of the distribution of oxidized DNA bases, we could show that photosensitization of DNA by BPDE involves electron abstraction (Type I) while tetraol acts mainly through singlet oxygen production (Type II). Under our experimental conditions, Type I was the major photosensitization process, which shows the lack of involvement of tetraol in the observed photo-oxidation reaction. Finally, we could show that the adducts, resulting from the alkylation of DNA by BPDE, are very potent sensitizers. Indeed, they are located in the close vicinity of the double helix and thus perfectly placed to induce oxidation reactions.

Ultraviolet A radiation potentiates the cytotoxic and genotoxic effects of 7H‐dibenzo[c,g]carbazole and its methyl derivatives

“…Consistent with our results, light‐induced DNA cleavage by PAH compounds was detected using plasmid DNA [Yu et al, ; Fu et al, ]. DNA breakage caused by co‐exposure of the carcinogen and UVA provides strong support for the role of hydroxyl radicals ( • ;OH), which are by‐products of photochemical reactions [Douki et al, ]. Hydroxyl radicals arise from the far less reactive superoxide radicals ( ), secondary products of Type I photosensitization mechanism, which are converted into H 2 O 2 via SOD before being reduced by transition metals such as ferrous and cuprous ions [Cadet and Douki, ].…”

Indenopyrene and Blue-Light Co-Exposure Impairs the Tightly Controlled Activation of Xenobiotic Metabolism in Retinal Pigment Epithelial Cells: A Mechanism for Synergistic Toxicity

“…Benzo[a]pyrene (BaP), a major high-molecular-weight PAH found in cigarette smoke, has been reported to sensitize DNA to oxidative damage in the presence of ultraviolet-A (UVA) radiation by producing ROS through both type I and II photosensitized oxidation reactions [51][52][53]. Thus, we first addressed IcdP photosensitization properties under HEV light in RPE cells (Figure 1).…”

Vitamin C prevents epidermal damage induced by PM‐associated pollutants and UVA1 combined exposure

“…totoxic even under blue light exposure. 9,13,20,21 Vitamin C protective effect observed in our experiments was therefore probably driven by the antioxidant potential of this compound. However, vitamin C also displays other effects as it may protect keratinocyte viability, improve chronic inflammation, overcome differentiationdependent oxidative stress and ensure function of skin barrier.…”