Ultraviolet A radiation potentiates the cytotoxic and genotoxic effects of 7H‐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.

Short-Term Ultraviolet A Irradiation Leads to Dysfunction of the Limbal Niche Cells and an Antilymphangiogenic and Anti-inflammatory Micromilieu

“…While UVA used to be considered as relatively innocuous, it now is emerging as a factor to mutagenesis 37 and damage to DNA, 38 proteins, and lipids, 39,40 thus associating it with cancer 41 and even dysregulation of immunity. 14 In ophthalmology, even though it is acceptable to use UVA for the treatment of keratoconus via collagen cross-linking, 42 studies have demonstrated that this technique becomes safer with the use of a protective ring around the limbal area to prevent damage to the stem cell compartment.…”

Corneal Collagen Cross-Linking With Riboflavin and UVA Regulates Hemangiogenesis and Lymphangiogenesis in Rats

“…The correspondence between the time-dependent immunostaining pattern changes and the variations in gene expression levels of the markers of hemangiogenesis and lymphangiogenesis confirm that CXL treatment only temporarily suppressed these two suture-induced responses in rat corneas. UVA exposure can induce mutagenesis 27 arising from DNA and protein damage. 28 Such alterations can induce cancer 29 and even dysregulated immunity.…”