Enhanced Unscheduled DNA Synthesis in UV-Irradiated Human Skin Explants Treated with T4N5 Liposomes

Yarosh, Daniel B.; Kibitel, Jeannie; Green, Lori A; Spinowitz, Alan L.

doi:10.1111/1523-1747.ep12479314

Cited by 33 publications

(14 citation statements)

References 13 publications

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“…This further prevents pyrimidine dimers that inhibit DNA replication, which are produced within duplex DNA upon ultraviolet (UV) exposure. In vitro and in vivo studies showed that DMC improves the repair of UV-irradiation-associated DNA [92,93]. …”

Section: Liposomal Formulations In Clinical Trialsmentioning

confidence: 99%

Liposomal Formulations in Clinical Use: An Updated Review

et al. 2017

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Liposomes are the first nano drug delivery systems that have been successfully translated into real-time clinical applications. These closed bilayer phospholipid vesicles have witnessed many technical advances in recent years since their first development in 1965. Delivery of therapeutics by liposomes alters their biodistribution profile, which further enhances the therapeutic index of various drugs. Extensive research is being carried out using these nano drug delivery systems in diverse areas including the delivery of anti-cancer, anti-fungal, anti-inflammatory drugs and therapeutic genes. The significant contribution of liposomes as drug delivery systems in the healthcare sector is known by many clinical products, e.g., Doxil®, Ambisome®, DepoDur™, etc. This review provides a detailed update on liposomal technologies e.g., DepoFoam™ Technology, Stealth technology, etc., the formulation aspects of clinically used products and ongoing clinical trials on liposomes.

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Section: Liposomal Formulations In Clinical Trialsmentioning

confidence: 99%

Liposomal Formulations in Clinical Use: An Updated Review

et al. 2017

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“…It was found that UVB-mediated immunosuppression, surface molecule expression and cytokine release could be reduced and prevented by applying T4N5 endonuclease, a bacteria-derived DNA repair enzyme (13)(14)(15). Penetration of T4N5 into cells was enabled by incorporation into liposomes, a route which allows T4N5 delivery both in vitro and in vivo (16). Similar observations were made with another repair enzyme, photolyase, which reverses cyclobutane pyrimidine dimers specifically upon illumination with photoreactivating light, a repair process called photoreactivation (17).…”

Section: Formation Of Sunburn Cells Is a Consequence Of Uv-induced Dnmentioning

confidence: 99%

Molecular mechanisms of UV‐induced apoptosis

Kulms

Schwarz

2000

Photoderm Photoimm Photomed

284

206

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Sunburn cells, single standing cells with typical morphologic features occurring in UV-exposed skin, have been recognized as keratinocytes undergoing apoptosis following UV irradiation. Induction of apoptosis following UV exposure appears to be a protective mechanism, getting rid off severely damaged cells that bear the risk of malignant transformation. UV-mediated apoptosis is a highly complex process in which different molecular pathways are involved. These include DNA damage, activation of the tumor suppressor gene p53, triggering of cell death receptors

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“…When topically applied to murine skin, T4N5 liposomes penetrate cells of the epidermis (13). The multilamellar lipid vesicles destabilize at low pH, thereby delivering the endonuclease intracellularly and increasing the rate of repair of pyrimidine dimers in DNA (14,15 …”

mentioning

confidence: 99%

Pyrimidine dimers in DNA initiate systemic immunosuppression in UV-irradiated mice.

Kripke

Cox

Alas

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

492

329

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Exposing the skin of mice to UV radiation interferes with the induction of delayed and contact hypersensitivity immune responses initiated at nonirradiated sites. The identity of the molecular target in the skin for these Immunosuppressive effects of UV radiation remains controversial. To test the hypothesis that DNA is the target for UV-induced systemic immunosuppression, we exposed C3H mice to UV radiation and then used liposomes to deliver a dimer-specific excision repair enzyme into the epidermis in situ. The application of T4 endonuclease V enulated in liposomes to UV-irradiated mouse skin decreased the number of cyclobutane pyrimidine dimers in the epidermis and prevented suppression of both delayed and contact hypersensitivity responses. Moreover, the formation of suppressor lymphoid cells was inhibited. Control, heat-inactivated endonuclease encapsulated in liposomes had no effect. These studies demonstrate that DNA is the major target of UV radiation in the generation of systemic immunosuppression and suggest that the primary molecular event mediating these types of immunosuppression by UV radiation is the formation of pyrimidine dimers. Furthermore, they illustrate that the delivery of lesion-specific DNA repair enzymes to living skin after UV Irradiation is an effective tool for restoring Immune function and suggest that this approach may be broadly applicable to preventing other alterations caused by DNA damage.Wavelengths of UV radiation in the middle, or UV-B (280-320 nm), range can impair a variety of immune responses in humans and laboratory animals both locally, within UVirradiated skin, and systemically, at distant sites (1). Exposure of mice to UV-B radiation interferes with the rejection of UV-induced skin cancers and the induction of delayed and contact hypersensitivity (DHS and CHS) responses initiated at unirradiated sites; these forms of immune suppression are associated with the induction of antigen-specific suppressor T lymphocytes (2). How UV-B radiation exerts its systemic, immunosuppressive effects is a question of considerable interest, both for understanding the regulatory pathways governing these immune responses and for assessing the potential effects of UV-B radiation on human health. The DHS response is particularly important in this regard because this T-lymphocyte-mediated immune reaction is responsible for protection against many chronic infectious diseases.Current experimental evidence implicates soluble substances derived from UV-irradiated keratinocytes as the probable mediators of UV-induced systemic suppression of DHS and CHS responses (3-5). However, the initial photobiological reaction responsible for triggering the cascade of events leading to activation of the suppressor pathway of the immune response remains controversial. Based on an in vivo action spectrum for systemic suppression of CHS in the mouse, it has been proposed that urocanic acid, a deamination product of histidine, present in the stratum corneum, is the photoreceptor for this form of UV-induce...

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Enhanced Unscheduled DNA Synthesis in UV-Irradiated Human Skin Explants Treated with T4N5 Liposomes

Cited by 33 publications

References 13 publications

Liposomal Formulations in Clinical Use: An Updated Review

Liposomal Formulations in Clinical Use: An Updated Review

Molecular mechanisms of UV‐induced apoptosis

Pyrimidine dimers in DNA initiate systemic immunosuppression in UV-irradiated mice.

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