CELLULAR-SENSITIVITY TO OXIDATIVE STRESS IN THE PHOTOSENSITIVITY DERMATITIS ACTINIC RETICULOID SYNDROME

Skin fibroblasts from certain patients with the photosensitivity derma titis/actinic reticuloid syndrome show enhanced sensitivity to ultravi olet radiation compared to normal fibroblasts. To probe further the li nk between oxidative damage and this disease, we have obtained a more extensive set of cell lines from patients with a severe form of the di sease and examined their sensitivity towards oxidative stress by measu ring cell survival following UVA radiation (330-450 nm) or hydrogen pe roxide treatment (0.1- 2.4 mM). The activation of the stress gene, hem e oxygenase, has also been assessed by measuring the accumulation of m RNA after hydrogen peroxide treatment. Our studies have confirmed that a slight ultraviolet sensitivity is a characteristic of photosensitiv ity dermatitis/actinic reticuloid syndrome cell strains and we further demonstrate that these cell lines are particularly sensitive to hydro gen peroxide with up to a three- to fourfold increased sensitivity as compared to normal controls. We also show that certain ataxia telangie ctasia strains that are especially sensitive to hydrogen peroxide are also slightly sensitive to ultraviolet radiation. Hydrogen peroxide in duces accumulation of mRNA for the oxidant-inducible stress protein, h eme oxygenase, with similar kinetics (maximum mRNA accumulation 2-4 h following treatment) and with a similar range of magnitudes in both no rmal (6.6 -20.6 times mRNA increase over basal levels) and photosensit ivity dermatitis/actinic reticuloid (2.9-12.8 times) skin cells. Becau se cells from photosensitivity dermatitis/actinic reticuloid patients show increased sensitivity towards oxidative stress but show no signif icant change in oxidant activation of the heme oxygenase gene, we prop ose that the defect involves a late stage of processing of oxidative d amage rather than a compromised free radical scavenging system.