Cellular sensitivity to oxidative stress in the photosensitivity dermatitis/actinic reticuloid syndrome.
ABSTRACT Skin fibroblasts from certain patients with the photosensitivity dermatitis/actinic reticuloid syndrome show enhanced sensitivity to ultraviolet radiation compared to normal fibroblasts. To probe further the link between oxidative damage and this disease, we have obtained a more extensive set of cell lines from patients with a severe form of the disease and examined their sensitivity towards oxidative stress by measuring cell survival following UVA radiation (330-450 nm) or hydrogen peroxide treatment (0.1-2.4 mM). The activation of the stress gene, heme oxygenase, has also been assessed by measuring the accumulation of mRNA after hydrogen peroxide treatment. Our studies have confirmed that a slight ultraviolet sensitivity is a characteristic of photosensitivity dermatitis/actinic reticuloid syndrome cell strains and we further demonstrate that these cell lines are particularly sensitive to hydrogen peroxide with up to a three- to fourfold increased sensitivity as compared to normal controls. We also show that certain ataxia telangiectasia strains that are especially sensitive to hydrogen peroxide are also slightly sensitive to ultraviolet radiation. Hydrogen peroxide induces accumulation of mRNA for the oxidant-inducible stress protein, heme oxygenase, with similar kinetics (maximum mRNA accumulation 2-4 h following treatment) and with a similar range of magnitudes in both normal (6.6-20.6 times mRNA increase over basal levels) and photosensitivity dermatitis/actinic reticuloid (2.9-12.8 times) skin cells. Because cells from photosensitivity dermatitis/actinic reticuloid patients show increased sensitivity towards oxidative stress but show no significant change in oxidant activation of the heme oxygenase gene, we propose that the defect involves a late stage of processing of oxidative damage rather than a compromised free radical scavenging system.
- SourceAvailable from: Jan-Olaf Gebbers[Show abstract] [Hide abstract]
ABSTRACT: Wound healing in fetal skin is characterized by the absence of scar tissue formation, which is not dependent on the intrauterine environment and amniotic fluid. Fetal cells have the capacity of extraordinary expansion and we describe herein the development of a fetal skin cell bank where from one organ donation (2-4 cm2) it is possible to produce several hundred million fetal skin constructs of 9 x 12 cm2. Fetal cells grow three to four times more rapidly than older skin cells cultured in the same manner and these banked fetal cells are very resistant against physical and oxidative stress when compared to adult skin cells under the same culture conditions. They are up to three times more resistant to UVA radiation and two times more resistant towards hydrogen peroxide treatment. This mechanism may be of major importance for fetal cells when they are delivered to hostile wound environments. For fetal cell delivery to patients, cells were associated with a collagen matrix to form a three-dimensional construct in order to analyze the capacity of these cells for treating various wounds. We have seen that fetal cells can modify the repair response of skin wounds by accelerating the repair process and reducing scarring in severe bums and wounds of various nature in children. Hundreds of thousands of patients could potentially be treated for acute and chronic wounds from one standardized and controlled cell bank.Cell Transplantation 02/2006; 15(8-9):823-34. · 4.42 Impact Factor
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ABSTRACT: Ataxia telangiectasia (AT) is a hereditary human disorder resulting in a wide variety of clinical manifestations, including progressive neurodegeneration, immunodeficiency, and high incidence of lymphoid tumors. Cells from patients with AT show genetic instability, hypersensitivity to radiation, and a continuous state of oxidative stress. Oxidative stress and genetic instability, including DNA deletions, are involved in carcinogenesis. We examined the effect of dietary supplementation with the thiol-containing antioxidant N-acetyl-l-cysteine (NAC) on levels of oxidative DNA damage and the frequency of DNA deletions in Atm-deficient (AT-mutated) mice. We confirmed that Atm-deficient mice display an increased frequency of DNA deletions (Bishop et al., Cancer Res 2000;60:395). Furthermore, we found that Atm-deficient mice have significantly increased levels of 8-OH deoxyguanosine, an indication of oxidative DNA damage. Dietary supplementation with NAC significantly reduced 8-OH deoxyguanosine level and the frequency of DNA deletions in Atm-deficient mice. These levels were similar to the levels in wild-type mice. Our findings demonstrate that NAC counteracts genetic instability and suggest that genetic instability may be a consequence of oxidative stress in Atm-deficient mice.Cancer Research 09/2004; 64(15):5148-53. · 8.65 Impact Factor
Article: Chronic actinic dermatitis[Show abstract] [Hide abstract]
ABSTRACT: Chronic actinic dermatitis is a photosensitive skin disease that most commonly affects elderly Caucasian males, but can also affect younger patients, particularly those with an atopic background. The clinical presentation is that of a recurrent dermatitis of the photo-exposed sites that can progress to a more lichenified and generalized appearance in the chronic phase. Investigation is best performed at specialist phototesting centers using monochromator phototesting and reveals broadband photosensitivity. Positive patch and/or photopatch testing to allergens is seen in approximately 75% of patients. The etiology of chronic actinic dermatitis has not yet been fully elucidated but a probable basis is that of delayed T-cell-mediated cellular hypersensitivity to an as yet unknown photo-induced antigen. The clinical treatment of chronic actinic dermatitis can be problematic and is focused around physical measures to prevent recurrent exacerbations and suppressive methods to limit the severity of such episodes. Immunosuppressants are often required and it is anticipated that future advances in molecular biology will allow the pathogenesis of the disease to be further understood, thereby facilitating more targeted treatment approaches.Expert Review of Dermatology 05/2006; 1(3):451-461.