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.
Keywords: 7H-dibenzo[c,g]carbazole; HaCaT cells; UVA light; oxidative damage to DNA; quantum-chemical descriptors of photoactivation; reactive oxygen species.
© 2014 Wiley Periodicals, Inc.