title: Ultraviolet A radiation potentiates the cytotoxic and genotoxic effects of 7 H-dibenzo[c,g]carbazole and its methyl derivatives.
abstract: 7H-Dibenzo[c,g]carbazole (DBC) is a heterocyclic aromatic hydrocarbon that is carcinogenic in many species and tissues. DBC is a common environmental pollutant, and is therefore constantly exposed to sunlight. However, there are limited data exploring the toxicity of DBC photoexcitation products. Here, we investigated the impact of ultraviolet (UV) A radiation on the biological activity of DBC and its methyl derivatives, 5,9-dibenzo[c,g]carbazole and N-methyl dibenzo[c,g]carbazole, on human skin HaCaT keratinocytes. Co-exposure of HaCaT cells to UVA and DBC derivatives resulted in a sharp dose-dependent decrease in cell survival and apparent changes in cell morphology. Under the same treatment conditions, significant increases in DNA strand breaks, intracellular reactive oxygen species, and oxidative damage to DNA were observed in HaCaT cells. Consistent with these results, an apparent inhibition in superoxide dismutase, but not glutathione peroxidase activity, was detected in cells treated with DBC and its derivatives under UVA irradiation. The photoactivation-induced toxicity of individual DBC derivatives correlated with the electron excitation energies approximately expressed as the energy difference between the highest occupied and the lowest vacant molecular orbital. Our data provide the first evidence that UVA can enhance the toxicity of DBC and its derivatives. Photoactivation-induced conversion of harmless chemical compounds to toxic photoproducts associated with reactive oxygen species generation may substantially amplify the adverse health effects of UVA radiation and contribute to increased incidence of skin cancer.
authors.affiliation: Laboratory of Mutagenesis and Carcinogenesis, Cancer Research Institute, SAS, Vlarska 7, Bratislava, Slovakia.
authors.forename: Eva
authors.initials: E
authors.lastname: Sedlačková
authors.forename: Andrea
authors.initials: A
authors.lastname: Bábelová
authors.forename: Katarína
authors.initials: K
authors.lastname: Kozics
authors.forename: Michal
authors.initials: M
authors.lastname: Šelc
authors.forename: Annamária
authors.initials: A
authors.lastname: Srančíková
authors.forename: Vladimír
authors.initials: V
authors.lastname: Frecer
authors.forename: Alena
authors.initials: A
authors.lastname: Gábelová
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002227:Carbazoles / Q000378:metabolism / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity; D002460:Cell Line / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012867:Skin / Q000166:cytology; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014466:Ultraviolet Rays / Q000009:adverse effects*; D000094765:Glutathione Peroxidase GPX1
chemical_list: D002227:Carbazoles; D002273:Carcinogens; D017382:Reactive Oxygen Species; C000606290:SOD1 protein, human; C041150:N-methyl-7H-dibenzo(c,g)carbazole; C039387:5,9-dimethyldibenzo(c,g)carbazole; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C013478:7H-dibenzo(c,g)carbazole; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human
keywords: 7H-dibenzo[c,g]carbazole; HaCaT cells; UVA light; oxidative damage to DNA; quantum-chemical descriptors of photoactivation; reactive oxygen species