Photochemistry and Photobiology

Biologically, light including ultraviolet (UV) radiations is vital for life. However, UV exposure does not come without risk, as it is a major factor in the development of skin cancer. This review discusses the beneficial and deleterious effects of solar exposure, including UV skin damage, Vitamin D production, circadian rhythm disruption and the impact of melatonin. Understanding of these benefits and risks is critical for the development of protective strategies against solar radiation.

Absorption of UVB photons by thymine and/or cytosine bases at bipyrimidine sites gives rise to cyclobutane pyrimidine dimers (CPDs) and (6-4) photoproducts (6-4PPs). The latter photoproducts can undergo UVA-mediated conversion into related Dewar valence isomers. CPDs are also produced by UVA through direct absorption, whereas oxidized bases and DNA strand breaks are generated by photosensitization mechanisms that may involve ¹O₂ (Type II) and formation of hydroxyl radical. Exogenous photosensitizers have been shown to modify DNA bases through various mechanisms, including Type I (one-electron oxidation), Type II, triplet–triplet energy transfer (TTET) and photocycloaddition as is the case for psoralen (pso) compounds.

Chronic skin exposure to ultraviolet (UV) radiation induces epigenetic modifications such that epigenetic mosaicism develops in patches of epidermal cells, which alters the levels of DNA methylation and histone acetylations. These epigenetic modifications in cells if not reversed or corrected may result in silencing of tumor suppressor genes and that will lead to the development of skin diseases including the development of melanoma and non-melanoma skin cancers. Topical application or consumption of dietary bioactive components may block, inhibit or slow down the progressing epigenetic alterations in cells exposed to UV radiation, and thus may result in prevention of the risk of skin cancers.

Regulation of skin pigmentation by solar radiation involves multiple signaling pathways in both melanocytes and keratinocytes. UVR stimulates the production of propiomelanocortin (POMC) and POMC-derived alpha–MSH (melanocyte stimulating hormone) within the keratinocyte through activation of p53. Alpha-MSH acts on the MC1R receptor on the melanocyte, stimulating the downstream cAMP pathway and expression of the melanocyte master regulator MITF, which activates transcription of the critical melanogenic enzymes, including tyrosinase. These enzymes synthesize melanin within the melanosomes and mature melanosomes are then exported to the keratinocyte where they form a perinuclear cap over the DNA protecting it from the effects of harmful radiation.

The interplay between antigen-presenting cell and effector T cell is important in determining the outcome of an immune response. Moreover, the optimal activation and expansion of an effector T cell is a net effect of the nature and strength of signals 1, 2 and 3. The chemopreventive agents act on these determinants of an immune response, namely, signals 1 through 3 and antigen-presenting cells, to modulate the immune response, thus resulting in effective control of tumor progression and aiding in tumor elimination.

The cutaneous epithelium of mammals is a complex dynamic tissue and undergoes continuous renewal throughout life. To date, several stem cell populations have been discovered and characterized in various skin lineages including interfollicular epidermis, and components of the hair follicle. However, key issues remain unresolved such as the identity of the target cells during nonmelanoma skin cancer. In this regard, the two stage skin chemical and UV radiation models have been useful for studying molecular carcinogenesis in detail. Significantly, transgenic mice have played an important role towards understanding the contribution of stem cells and their lineages during carcinogenesis such that there are now several reports confirming at least one population of stem cells as target cells in nonmelanoma skin cancer. Nevertheless, the role of other cell types and non-stem cells during cancer initiation, promotion, and progression cannot be ignored.

UV radiation-induced assembly of inflammasomes in keratinocytes can result in the release of different pro-inflammatory IL-1-family mediators that have distinct influences on the development of the adaptive arm of cutaneous immune responses, depending on the extent of UV damage.. Precursor IL-1β and IL-18 cytokines require caspase-1 activity in the inflammasome complex for their maturation and secretion. In contrast, the other IL-1 family members, IL-1α and IL-33 are normally sequestered in the cell nucleus and released as “alarmins” through unconventional caspase-1-dependent secretion. Different DAMPs activate TLR-induced transcription and NLR-induced formation of inflammasomes that result in the secretion of IL-1 family mediators that have distinct influences on different T-cell subsets.

Solar UV radiation, particularly its UVB component (280–320 nm), causes adverse cellular and molecular events leading to skin cancer. Therefore, additional approaches are needed to define novel agents to prevent skin cancer which results as a consequence of UVB exposure. In this study, we investigated the photochemopreventive effects of pomegranate fruit extract (PFE) after multiple UVB irradiations to the skin of SKH-1 hairless mice. Our data show that PFE consumption afforded protection to mouse skin by inhibiting UVB-induced inflammation and proliferation via modulation of nuclear factor kappa B and mitogen-activated protein kinases pathways. This study suggests the potential efficacy of PFE as a photochemopreventive agent for skin cancer.

UVA radiation causes significant damage to cellular components through the release of reactive oxygen species (ROS). We report that silibinin enhances UVA-induced ROS generation and apoptosis in human keratinocyte HaCaT cells. Furthermore, we found that silibinin enhances ER stress-mediated apoptosis in HaCaT cells by increasing the expression of CHOP protein. These results suggest that silibinin may be beneficial in the removal of UVA-damaged cells and the prevention of skin cancer.

UVB induces skin inflammation and tumors, which is mediated by the activation of multiple pathways. Inducible nitric oxide synthase and cyclooxygenase-2 induced by UVB are important mediators of inflammation. Chronic skin exposure to UVB induces benign lesions known as papillomas. A fraction of papillomas progress to invasive squamous cell carcinoma (SCC), perhaps through the process of epithelial-mesenchymal transition (EMT). UVB induces a decrease in epithelial polarity regulating E-cadherin and an increase in mesochyme regulating proteins. NO-sulindac, a nitric oxide releasing NSAID blocks tumorigenesis by reducing proliferation and inducing apoptosis. It also targets EMT and reduces SCC incidence in murine skin.

Metformin blocks skin cancer pathogenesis by targeting various pathways: Treatment with metformin reduced progression of cutaneous SCCs by targeting multiple pathways. Metformin reduces proliferation, inflammation and cell survival regulatory signaling and induces apoptosis.

Skin exposure to ultraviolet light stimulates the production of cytokines known to be involved in the initiation of skin cancer. Immunohistochemical analysis revealed an enhanced expression of macrophage migration inhibitory factor (MIF) in lesional skin of patients with UV-induced actinic keratosis or cutaneous squamous cell carcinoma (SCC). ELISA studies showed a time-dependent increase in MIF secretion after a single-dose UVB irradiation in NHEK and SCC tumor cells. MIF receptor CD74 is not constitutively expressed in keratinocytes but stimulation with IFNγ upregulated CD74 surface expression. These findings indicate that MIF may be an important factor in the pathogenesis of NMSC tumorigenesis.

Resveratrol-induced premature senescence is associated with aberrant autophagic process in A431 cells in which resveratrol blocks autolysosome formation via the downregulation of Rictor-mediated RhoA-GTPase activity, leading to actin cytoskeleton reorganization. Rictor is overexpressed in UV-induced murine SCCs, whereas resveratrol decreases the level of Rictor and induces senescence in SCCs. This suggests that the downregulation of Rictor might serve as a mechanism of tumor suppression associated with premature senescence.

Hairless (HR) and NFκB form a positive feedback loop that can be initiated by UVB stimulation and is sustained by UVB-induced TNFα. In normal human keratinocytes, HR expression is elevated immediately following UVB irradiation and comprises part of the early UVB keratinocytic response mechanism leading to increased levels of activated NFκB. In the later UVB response, NFκB activation escalates TNFα secretion that downregulates HR expression via direct binding of the p65 subunit of NFκB to the HR promoter. Therefore, in HR mutant keratinocytes, NFκB is constitutively activated with downstream consequences for cell survival, proliferation and differentiation.

Much of the information in the literature defining the aberrations in signal transduction pathways induced by ultraviolet (UV) A and B cannot cross talk because of physiologically incompatible light dosimetry, and use of different cell populations. The aim of this study was to establish, in normal epidermal keratinocytes, at physiologically relevant doses, the expression profiles of cell signaling molecules in response to UVA and UVB irradiation. These findings will help delineate the differential effects of UV irradiation on the human skin and may have implications for interventions against signaling events mediated by UVA and UVB.

Alterations in lipid content, especially the elevation of cholesterol caused by UVB irradiation leads to activation of the Fas-FADD cascade and cell apoptosis. Depending on the cell type, a disruption of lipid rafts by MβCD could protect cells from UVB-induced apoptosis, but might also promote nonapoptotic death of the treated cells.

Malaysian tualang honey possesses strong antioxidant and anti-inflammatory properties. We found that treatment of tualang honey inhibited ultraviolet (UV) B-induced DNA damage, and enhanced repair of UVB-mediated formation of cyclobutane pyrimidine dimers and 8-oxo-7,8-dihydro-2′-deoxyguanosine in murine keratinocyte cell line PAM212. Treatment of tualang honey inhibited UVB-induced activation of NF-κB, inflammatory cytokines and inducible nitric oxide synthase. Furthermore, the treatment of tualang honey inhibited UVB-induced COX-2 expression and PGE2 production. Taken together, we provide evidence that the treatment of tualang honey to keratinocytes affords substantial protection from the adverse effects of UVB radiation via modulation in early biomarkers of photocarcinogenesis.

Bi₂O₃ and rare earth (La, Ce)-doped Bi₂O₃ visible-light-driven photocatalysts were synthesized in a Triton X-100/n-hexanol/cyclohexane/water reverse microemulsion. The as-prepared catalysts were characterized by X-ray powder diffraction (XRD), transmission electron microscopy (TEM), Brunauer–Emmett–Teller (BET) surface area, photoluminescence spectra (PLS) and UV–Vis diffuse reflectance spectroscopy. The photocatalytic activity of the samples was evaluated by degradation of methyl orange (MO) and 2,4-dichlorophenol (2,4-DCP) under visible light (λ > 420nm) irradiation. The mechanisms of influence on the photocatalytic activity of the catalysts were discussed

Effective transmission of liquid and solid samples commonly used in cell cultures. Among the most commonly used wavelengths in low-level laser therapy (633–690 nm), the lowest absorption coefficients were reached by Dulbecco’s modified Eagle’s medium and Roswell Park Memorial Institute, which reach an effective transmission of 93% of incident radiation. Among the solid materials in the same range of the electromagnetic spectrum, the lowest absorption coefficient was obtained for the polystyrene (Petri dish and well plate), with 78% of effective transmission.

Exposure of silk to UV light affects physical properties of the fabric, such as strength and elasticity and causes yellowing. Photoproducts of tyrosine are characterized and the extend of photodegradation is correlated with changes in coloration by assigning each individual observed oxidative modification within the peptide a score based on the relative level of the modification. Tin weighting was a common method used from the late 18th century to the early 20th century for replacing weight lost during degumming of silk. It causes fibrillation and fractures and intensifies yellowing under UV irradiation.

The present study was undertaken to assess the effect of He-Ne laser irradiation (5–40 J cm⁻²) on in vitro seed germination, physiological and biochemical changes in the seedlings of eggplant (Solanum melongena L.) var. Mattu Gulla, a unique variety being cultivated in Mattu Village, Udupi, Karnataka, India. The results indicated improved in vitro germination of seeds, growth, physiological and biochemical characteristics in seedlings of eggplant at 25 and 30 J cm⁻² of laser irradiation. The established method could be used for pre-sowing treatment of eggplant seeds with laser rays for enhanced germination and growth.

Photoinduced reactions of 2′-deoxyuridine, 2′-deoxycytidine, 5-methyl-2′-deoxycytidine and 5-bromo-2′-deoxyuridine (5-BrdUrd) have been studied. For each compound, a number of previously undescribed cyclobutane dimers (CBDs) have been isolated and structurally characterized; the structures of the CBDs formed by 5-BrdUrd, along with the previously characterized dU–dU, are shown in the accompanying Scheme. Partial characterizations of (X-4)-type adducts of the same four nucleosides are also described (X = 5 or 6). Evidence is provided that 5-iodo-2′-deoxyuridine (5-IdUrd), 5′-bromo-2′-deoxyctytidine and 5-iodo-2′-deoxycytidine also react photochemically to form CBDs and that 5-BrdUrd and 5-IdUrd react photochemically with thymidine to form mixed CBDs and/or (X-4) adducts.

Photophysical properties of Norfloxcacin (NOR) and Ofloxacin (OFL) have been investigated in bile salts aggregates. Excitation at shorter wavelengths causes a quenching in emission intensity, whereas excitation at longer wavelength increases the emission intensity with addition of deoxycholate, taurocholate (TC) and glycodexoycholate salts. The excess hydronium ions in the hydrophilic surface of bile salt aggregates convert the neutral species of NOR and OFL into a cationic species, which causes an enhancement in the emission intensity. Glycodeoxycholate and TC because of the conjugate head group are more effective in converting the neutral species of fluoroquinolones into a cationic species.

Equilibrium serum protein distribution of liposomal mTHPC is identical to solvent-based drug. PEGylated liposome-based mTHPC has higher stability in serum than conventional-based. Foslip^® and Fospeg^® do not show significant aggregation in serum. Inclusion of mTHPC into liposomes increases their stability in serum. At short incubation times the redistribution of mTHPC from Foslip^® and Fospeg^® proceeds by both drug release and liposomes destruction. At longer incubation times, the drug redistributes only by release.

We studied the interaction between a phosphatidylinositol 3-kinases (PI3K) pathway inhibitor NVP-BEZ235 (BEZ235) and photodynamic therapy (PDT) with photosensitizer verteporfin in SVEC endothelial and PC-3 prostate cancer cells. Our results demonstrated that BEZ235 in combination with verteporfin resulted in enhanced cell growth inhibition in both cell lines. The combination therapy induced greater inhibition of PI3K signaling than each individual therapy.

We examined effects of fluence rate on photobleaching of the photosensitizer Pc 4 during photodynamic therapy (PDT) and the relationship between photobleaching and tumor response to PDT. Tumor-bearing mice were given Pc 4 by intratumor injection and irradiated at 667 nm with an irradiance of 50 or 150 mW cm⁻² up to 100 J cm⁻². No significant correlation was found between photobleaching and tumor regrowth for the data interpreted as a whole. Within each group, weak associations between photobleaching and outcome were observed. It appears that Pc 4 photobleaching is not a strong predictor of tumor response to Pc4-PDT under these conditions.

The antimicrobial properties of visible light is an area of increasing interest. This study investigates for the first time the sensitivity of the important bacterial foodborne pathogen Listeria monocytogenes to selected wavelengths of visible light, demonstrating that the optimum wavelength for inactivation was 405(±5) nm. Comparative data for the 405 nm light inactivation of L. monocytogenes, and other Listeria species, with other important foodborne pathogens including Escherichia coli, Salmonella enteritidis and Shigella sonnei, are also presented, with Listeria species showing higher susceptibility to inactivation through 405 nm light exposure.

This study explored the effects of two photochemical inactivation methods (methylene and riboflavin, MB and RB) on hepatitis B virus (HBV) immunogenicity. The results indicated that the secretion of IFN-γ and TNF-α were upregulated following MB. The inactivation of HBV could upregulate the Th1-type cellular immune responses, which may play significant roles in the antiviral process.

The proteoglycan biglycan, immunostaining in red, is expressed in extracellular bone matrix and seem to play a role in bone cell differentiation and proliferative activity. It has been proposed that modulate local storage and/or availability of different growth factors including transforming growth factor (TGF). Our data show the presence of biglycan peaking at day 8 for both experimental conditions. Furthermore, LLLT leads to an increase in the expression of biglycan.