Repeated exposures of human skin equivalent to low doses of ultraviolet-B radiation lead to changes in cellular functions and accumulation of cyclobutane pyrimidine dimers

Abstract

Chronic exposure to sunlight may induce skin damage such as photoaging and photocarcinogenesis. These harmful effects are mostly caused by ultraviolet-B (UVB) rays. Yet, less is known about the contribution of low UVB doses to skin damage. The aim of this study was to determine the tissue changes induced by repeated exposure to a suberythemal dose of UVB radiation. Human keratinocytes in monolayer cultures and in skin equivalent were irradiated daily with 8 mJ/cm2 of UVB. Then structural, ultrastructural, and biochemical alterations were evaluated. The results show that exposure to UVB led to a generalized destabilization of the epidermis structure. In irradiated skin equivalents, keratinocytes displayed differentiated morphology and a reduced capacity to proliferate. Ultrastructural analysis revealed, not only unusual aggregation of intermediate filaments, but also disorganized desmosomes and larger mitochondria in basal cells. UVB irradiation also induced the secretion of metalloproteinase-9, which may be responsible for degradation of type IV collagen at the basement membrane. DNA damage analysis showed that both single and repeated exposure to UVB led to formation of (6-4) photoproducts and cyclobutane pyrimidine dimers. Although the (6-4) photoproducts were repaired within 24 h after irradiation, cyclobutane pyrimidine dimers accumulated over the course of the experiment. These studies demonstrate that, even at a suberythemal dose, repeated exposure to UVB causes significant functional and molecular damage to keratinocytes, which might eventually predispose to skin cancer.

Infliximab inhibits DNA repair in ultraviolet B‐irradiated premalignant keratinocytes

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Irritant contact dermatitis: A review

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The Endogenous Protease Inhibitor TIMP-1 Mediates Protection and Recovery from Cutaneous Photodamage

“…Animal models and human skin substitutes are frequently used in studies evaluating skin photodamage and photoaging. However, results from those studies may be misleading because of their inferior architectures, exemplified by relatively thin epidermal layers and compromised barrier functions (Chouinard et al, 2001). The use of human skin should be more appropriate for studying skin photoaging (Kang et al, 1997;El-Domyati et al, 2002), and therefore we previously established a comprehensive photodamaged/ photoaged skin model using human skin xenografted onto severe combined immunodeficient (SCID) mice .…”