UVA Irradiation of Dysplastic Keratinocytes: Oxidative Damage versus Antioxidant Defense

Abstract

UVA affects epidermal cell physiology in a complex manner, but the harmful effects have been studied mainly in terms of DNA damage, mutagenesis and carcinogenesis. We investigated UVA effects on membrane integrity and antioxidant defense of dysplastic keratinocytes after one and two hours of irradiation, both immediately after exposure, and 24 h post-irradiation. To determine the UVA oxidative stress on cell membrane, lipid peroxidation was correlated with changes in fatty acid levels. Membrane permeability and integrity were assessed by propidium iodide staining and lactate dehydrogenase release. The effects on keratinocyte antioxidant protection were investigated in terms of catalase activity and expression. Lipid peroxidation increased in an exposure time-dependent manner. UVA exposure decreased the level of polyunsaturated fatty acids, which gradually returned to its initial value. Lactate dehydrogenase release showed a dramatic loss in membrane integrity after 2 h minimum of exposure. The cell ability to restore membrane permeability was noted at 24 h post-irradiation (for one hour exposure). Catalase activity decreased in an exposure time-dependent manner. UVA-irradiated dysplastic keratinocytes developed mechanisms leading to cell protection and survival, following a non-lethal exposure. The surviving cells gained an increased resistance to apoptosis, suggesting that their pre-malignant status harbors an abnormal ability to control their fate.

Antioxidant Status and Oxidative Stress in Patients with Chronic ITP

“…All antioxidants or the total antioxidant status (TAS) is often used to estimate the overall antioxidative status. Likewise, total oxidant status (TOS) is measured to determine a patient's overall oxidation state [30].…”

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.…”

Sea-Buckthorn Seed Oil Induces Proliferation of both Normal and Dysplastic Keratinocytes in Basal Conditions and under UVA Irradiation

“…These cells are characterized by atypical nuclei and disorganized growth, leading to precancerous skin lesions [ 13 ]. Evidence demonstrates that UVA irradiation of dysplastic keratinocytes has detrimental effects in the first few hours of exposure, but long-term, it activates cell protection and survival mechanisms [ 14 ], aggravating their malignant potential. Additionally, malignancy was previously shown to be aggravated by alterations in cellular lipid metabolism [ 15 , 16 ] to favor cell survival and proliferation.…”