Sunscreens and T4N5 Liposomes Differ in Their Ability to Protect Against Ultraviolet-Induced Sunburn Cell Formation, Alterations of Dendritic Epidermal Cells, and Local Suppression of Contact Hypersensitivity

Peter Wolf, Patricia Cox, Daniel B. Yarosh, Margaret L. Kripke
1995 Journal of Investigative Dermatology  
Exposure of skin to ultraviolet (UV) radiation can lead to diverse biologic effects, including inflammation, sunburn cell formation, alterations of cutaneous immune cells, and impaired induction of contact hypersensitivity responses. The molecular mechanisms of these UV -induced effects are not completely understood. We investigated the ability of sunscreens and liposomes containing the DNA excision repair enzyme T 4 endonuclease V to prevent these effects of UV radiation. The use of T4N5
more » ... mes, which increase the repair of cyclobutyl pyrimidine dimers, provides an approach for assessing the role of DNA damage in the effects of UV radiation on the skin. Exposing C3H mice to 500 mJ/cm2 UVB radiation from FS40 sunlamps resulted in skin edema, sunburn cell formation, and morphologic alterations and decreased numbers of Langerhans cells and Thy-l + dendritic epidermal T cells. In addition, the induction of contact hypersensitivity after application of 2,4-dinitrofluorobenzene on UV -irradiated skin was Itraviolet (UV) radiation has potentially hazardous biolo gic effects on skin, including induction of skin cancer [1 ]. In laboratory animals, UV radiation can act as a tumor initiator [2], a tumor promotor [3], and a co-carcinogen by causing immune suppression [4, 5] . Exposure of mice to UV radiation impairs the induction of immune responses to UV-induced skin cancers [6] and, in a similar manner, to contact-sensitizing haptens [7] . Evidence also suggests that UV radiation contributes to skin cancer formation in cells; T4N5 liposomes, liposomes containing active T4 endonuclease V. diminished by 80%. Applying sunscreens containing octyl-N-dimethyl-p-aminobenzoate, 2-ethyihexyl-pmethox ycinnamate, or benzophenone-3 before this dose of UV irradiation gave nearly complete protection against all of these effects of UV irradiation. In contrast, topical application ofT4N5 liposomes after UV irradiation had no effect on UV -induced skin edema and only partially protected against sunburn cell formation and local suppression of contact hypersensitivity, although its ability to protect against alterations in dendritic immune cells was comparable to that of the sunscreens. These results suggest that DNA damage is involved in only some of the local effect s ofUV radiation on the skin. In addition, T4N5 liposomes may be a useful adjunct to sunscreens because they can reduce some of the deleterious effects of UV radiation on skin even after a sunburn has been initiated. Key words: UVB/cydobutyl pyrimidine dimers/DNA repair/immune suppression/photoimmunology/ photoprotection. J Invest D ermatol 104:287-292, 1995 humans through its effects on the immune system, as well as by its direct carcinogenic effect on cells in the skin [8 -1 0]. How UV irradiation leads to suppressed immune responses is not completely understood. However, UV-induced local immune suppression is accompanied by a decrease in the number of antigenpresenting Langerhans cells and Thy-1 + dendritic epidermal T cells (DETC) in the skin, and an increase in CD11 b + macrophages [11] [12] [13] . Contact sensitization through UV-irradiated skin is associated with the appearance of hapten-specific T -suppressor lymphocytes in the spleen [12, 14] . The release of soluble factors such as prostaglandins [15], tumor necrosis factor-a [16], interleukin-1 [15], contra-interleukin-1 [17], and interleukin-10 [18], and the formation of cis-urocanic acid [16,19], all may contrib ute to immune suppression. At the molecular level, there is evidence that DNA damage is involved in many biologic effects ofUV radiation. Most important, in the genetic disease xeroderma pigmentosum, a deficiency in r epairing UV -indu ced DNA d amage is associated with an extraordinarily high incidence of skin can cer [20] . Sunscreens, which reduce UV-induced DNA damage [21] [22] [23] , are highly protective 0022-202X/95/$09.50 • SSDI0022-202X(94)00279-G • Copyrigh t
doi:10.1111/1523-1747.ep12612828 pmid:7829886 fatcat:ay6j5rzo7bg5ldukyn6svwxkye