Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exposure of skin to ultraviolet (UV) radiation inhibits the induction of delayed-type hypersensitivity (DTH) responses initiated at a distant, unirradiated site. Recent studies attributed this form of immune suppression to DNA damage in the form of cyclobutane pyrimidine dimers (CPD). In the present study, we investigated the protective defects of sunscreens on UV-induced systemic suppression of DTH to Candida albicans, inflammation, and DNA damage. The photoprotective effects of sunscreen preparations containing 8% octyl-N-dimethyl-p-aminobenzoate, 7.5% 2-ethylhexyl-p-methoxycinnamate, or 6% benzophenone-3 were studied in C3H mice exposed to a single dose of 500 mJ/cm2 UVB radiation from FS40 sunlamps. Inflammation was determined by the amount of skin edema at the site of UV irradiation, and DNA damage was assessed by measuring the frequency of endonuclease-sensitive sites in the epidermis. Application of the sunscreens before UV irradiation gave 75-97% protection against UV-induced edema, 67-91% protection against formation of CPD, but only 30-54% protection against suppression of DTH. In contrast, the topical application of liposomes containing a CPD-specific DNA repair enzyme immediately after UV irradiation resulted in 82% protection against suppression of DTH, but at best, 39% protection against skin edema. These findings demonstrate that sunscreens give less protection against UV-induced immune suppression than against skin edema and CPD formation. Furthermore, they suggest that less DNA damage is required to cause UV-induced immune suppression than to cause sunburn.
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PMID:Effects of sunscreens and a DNA excision repair enzyme on ultraviolet radiation-induced inflammation, immune suppression, and cyclobutane pyrimidine dimer formation in mice. 840 17

On illumination with simulated sunlight, the UVB-absorbing sunscreen chemical 2-ethylhexyl-4-dimethylaminobenzoate (Padimate-O) generates excited species which inflict non-ligatable strand breaks on DNA in vitro and it also becomes mutagenic to yeast in vivo. Padimate-O is known to penetrate human skin but its effects on human cells are not clear. Here, we first simulate the sunlight which penetrates human skin and use it to illuminate human keratinocytes. The DNA damage observed in terms of UV-endonuclease-sensitive sites (ESS) and direct strand breaks per kilobase (kb) of DNA per joule per square metre agrees well with that predicted from action spectra based on monochromatic light. Using plasmid DNA in vitro, we find a very similar pattern of results. Next, we simulate the spectrum that results when the incident light is first attenuated by a film of sunscreen (SPF-15; 2 mg/cm(2)) containing benzophenone-3 (a UVA absorber), octyl methoxycinnamate (a UVB absorber), and Padimate-O. If the sunscreen is not in contact with keratinocytes it reduces direct DNA damage from sunlight (ESS). However, any Padimate-O in contact with the cells substantially increases indirect damage (strand breaks) even though the film of sunscreen reduces direct photodamage. We estimate that applying an SPF-15 sunscreen which contains Padimate-O to human skin followed by exposure to only 5 minimum erythemal doses (MED) of sunlight could, while suppressing the formation of ESS, increase strand breaks in cells under the epidermis by at least 75-fold compared to exposure to 1 MED in the absence of sunscreen.
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PMID:Illumination of human keratinocytes in the presence of the sunscreen ingredient Padimate-O and through an SPF-15 sunscreen reduces direct photodamage to DNA but increases strand breaks. 1047 39