Abstract:Sunlight’s ultraviolet wavelengths induce cyclobutane pyrimidine dimers (CPDs), which then cause mutations that lead to melanoma or to cancers of skin keratinocytes. In pigmented melanocytes, we found that CPDs arise both instantaneously and for hours after UV exposure ends. Remarkably, the CPDs arising in the dark originate by a novel pathway that resembles bioluminescence but does not end in light: First, UV activates the enzymes nitric oxide synthase (NOS) and NADPH oxidase (NOX), which generate the radical… Show more
“…Furthermore, this study was not designed to determine sunscreen DNA-PF, which is an important parameter for future research. Prevention of CPD provides a mechanistic basis for the ability of sunscreens to inhibit SCC, and possibly melanoma (48). Our data support the role of regular sunscreen use to reduce the risk of skin cancer and the application of very high SPF sunscreens, even if they are typically used at ~1/3 of the thickness required for SPF labelling.…”
The cyclobutane pyrimidine dimer (CPD) is a potentially mutagenic DNA photolesion that is the basis of most skin cancers. There are no data on DNA protection by sunscreens under typical conditions of use. The study aim was to determine such protection, in phototypes I/II, with representative sunscreen-user application. A very high SPF formulation was applied at 0.75, 1.3 and 2.0 mg/cm2. Unprotected control skin was exposed to 4 standard erythema doses (SED) of solar simulated UVR, and sunscreen-treated sites to 30 SED. Holiday behaviour was also simulated by UVR exposure for 5 consecutive days. Control skin received 1 SED daily, and sunscreen-treated sites received 15 (all 3 application thicknesses) or 30 (2.0 mg/cm2) SED daily. CPD were assessed by quantitative HPLC-tandem mass spectrometry (HPLC-MS/MS) and semi-quantitative immunostaining. In comparison with unprotected control sites, sunscreen significantly (p ≤ 0.001-0.05) reduced DNA damage at 1.3 and 2.0 mg/cm2 in all cases. However, reduction with typical sunscreen use (0.75 mg/cm2) was non-significant, with the exception of HPLC-MS/MS data for the 5-day study (p <0.001). Overall, these results support sunscreen use as a strategy to reduce skin cancer, and demonstrate that public health messages must stress better sunscreen application to get maximal benefit.
“…Furthermore, this study was not designed to determine sunscreen DNA-PF, which is an important parameter for future research. Prevention of CPD provides a mechanistic basis for the ability of sunscreens to inhibit SCC, and possibly melanoma (48). Our data support the role of regular sunscreen use to reduce the risk of skin cancer and the application of very high SPF sunscreens, even if they are typically used at ~1/3 of the thickness required for SPF labelling.…”
The cyclobutane pyrimidine dimer (CPD) is a potentially mutagenic DNA photolesion that is the basis of most skin cancers. There are no data on DNA protection by sunscreens under typical conditions of use. The study aim was to determine such protection, in phototypes I/II, with representative sunscreen-user application. A very high SPF formulation was applied at 0.75, 1.3 and 2.0 mg/cm2. Unprotected control skin was exposed to 4 standard erythema doses (SED) of solar simulated UVR, and sunscreen-treated sites to 30 SED. Holiday behaviour was also simulated by UVR exposure for 5 consecutive days. Control skin received 1 SED daily, and sunscreen-treated sites received 15 (all 3 application thicknesses) or 30 (2.0 mg/cm2) SED daily. CPD were assessed by quantitative HPLC-tandem mass spectrometry (HPLC-MS/MS) and semi-quantitative immunostaining. In comparison with unprotected control sites, sunscreen significantly (p ≤ 0.001-0.05) reduced DNA damage at 1.3 and 2.0 mg/cm2 in all cases. However, reduction with typical sunscreen use (0.75 mg/cm2) was non-significant, with the exception of HPLC-MS/MS data for the 5-day study (p <0.001). Overall, these results support sunscreen use as a strategy to reduce skin cancer, and demonstrate that public health messages must stress better sunscreen application to get maximal benefit.
“…Recently, triplet‐excited carbonyl compounds have been linked to possible melanoma incidence . DNA photoproducts are formed almost immediately after thymine or cytosine absorb UV‐light, but cyclobutane pyrimidine dimer generation in melanocytes still occurs hours after UVA exposure has ended . Sorbate inhibits 9,10‐dibromoanthracene‐2‐sulphonate (DBAS)‐enhanced chemiluminescence and cyclobutane pyrimidine dimer formation, a clear indication of the involvement of triplet species in the latter process.…”
Section: The (Bio)chemistry Of Four‐membered Ring Peroxidesmentioning
Four-membered cyclic peroxides are high-energy compounds often associated to cold light emission, but whose chemical and biological roles are still matters of debate. The often-dangerous synthesis of 1,2-dioxetanes, achieved around 50 years ago, has been mastered over the years to a point where some derivatives are commercially available. This fact does not imply that 1,2-dioxetanes can be conveniently prepared in the gram scale or that the synthesis of analogous 1,2-dioxetanones and the elusive 1,2-dioxetanedione are simple. Important questions on the mechanism of chemiluminescence and bioluminescence reactions are under experimental and theoretical scrutiny. The available data have contributed to relate structural and medium effects to the quantum efficiency of these compounds to produce excited states. Consequently, such peroxides have been suggested to produce biologically relevant electronically excited species in vivo in the absence of light. The connection of this hypothesis with melanin-mediated photodamage in the dark has renewed the interest in such cyclic peroxides. This review gives some insight on the synthesis, chemiluminescence mechanism, and biological relevance of 1,2-dioxetanes, 1,2-dioxetanones, and 1,2-dioxetanedione and provides practical protocols for those interested in engaging this field.
“…A strong electron stimulation of melanin occurring under the influence of UV and free oxygen radicals, called chemiexcitation, was first found in mammals and just in melanocytes. It is analogous to the chemical reaction used by fireflies in the production of light [19]. Chemical excitation of melanin by reactive electrons generates a new important source of genome instability and theoretically can occur everywhere where melanin exists and ROS are generated.…”
Parkinson's disease (PD) is a neurodegenerative disorder, characterised by depletion of dopamine in the striatum and loss of melanin-positive, dopaminergic neurons in the substantia nigra. Melanoma is a skin neoplasm arising from epidermal melanocytes. The epidemiology of melanoma focuses on well-known risk factors such as light skin and hair colour, gender, eye pigmentation, and ultraviolet (UV) exposure. Many studies have suggested an association between Parkinson's disease and melanoma. The mechanism underlying the possible connection between PD and melanoma is not clear and has aroused lots of interest. More interesting is that the link between these two diseases runs both ways. What is the underlying cause of this reciprocal association?Is it due to Parkinson's treatment? Is levodopa the reason for increased incidence of melanoma in people with the neurodegenerative condition? Are there any genetic, immune system irregularities or environmental risk factors that serve as the common denominator between these two conditions? Should we consider melanoma comorbidity with Parkinson's disease and vice versa? Some hypotheses include pigmentation changes in melanin and/or melanin synthesis enzyme like tyrosinase hydroxylase, autophagy deficits, disturbed form of metabolically controlled cell death, and changes of PD-related genes such as Parkin or a-synuclein. Learning more about the relationship between PD and melanoma may lead to a better understanding of each disease and contribute to more effective treatments of both.
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