UVA exposure affects UVB and cis-urocanic acid-induced systemic suppression of immune responses in Listeria monocytogenes-infected Balb/c mice

Ultraviolet radiation can inhibit immune responses locally as well as systemically. Such effects have been measured in animals and humans exposed to ultraviolet B (wavelength 280-315 nm) (UVB) and ultraviolet A (315-400 nm) (UVA). The precise wavelength dependence is important for the identification of possible molecular targets and for assessments of risk of different artificial UV sources and solar UV. In such analyses, it is commonly assumed that radiation energy from each wavelength contributes to the effect independent of the other wavelengths. Here we show that this assumption does not hold good. In the present study, it was investigated whether exposure to broadband UVA or longwave ultraviolet A 1 (340-400 nm) (UVA 1) prior to the standard immunosuppressive UVB protocol might modulate the immunosuppressive effects induced by UVB. Preexposure to broadband UVA or longwave UVA 1, 1 day prior to the standard immunosuppressive UVB protocol, inhibited the UVB-induced suppression of delayed type hypersensitivity (DTH) to Listeria monocytogenes significantly. This effect was not associated with restoring the number of interleukin (IL-12)-positive cells in the spleen. Since isomerization of trans-urocanic acid (UCA) into the immunosuppressive cis-UCA isomer plays a crucial role in UVB-induced immunomodulation, in a second set of experiments it was investigated whether immunosuppression induced by cis-UCA might also be downregulated by preexposure to UVA. Animals were exposed to broad-band UVA or longwave UVA 1 prior to application of an immunosuppressive dose of cis- or trans-UCA as a control. Both UVA and UVA 1 appear to inhibit the cis-UCA-induced systemic immunosuppression (DTH and IL-12) to L. monocytogenes. These studies clearly show that UVA radiation modulates both UVB and cis-UCA-induced immunomodulation. In general, our studies indicate that both broadband UVA and longwave UVA 1 could induce modulation of UVB and cis-UCA-induced immunomodulation. As sunlight contains both UVA and UVB radiation the balance between these two radiations apparently determines the net immunomodulatory effect.     

LACK OF CORRELATION BETWEEN SUPPRESSION OF CONTACT HYPERSENSITIVITY BY UV RADIATION AND PHOTOISOMERIZATION OF EPIDERMAL UROCANIC ACID IN THE HAIRLESS MOUSE

Abstract The immunological consequences of exposure to UVA (320–400 nm) radiation are unclear. This study describes the relationship between the generation of epidermal cis -urocanic acid and the ability to respond to a contact-sensitizing agent, in hairless mice exposed to different UV radiation sources, which incorporate successively greater short-wavelength cutoff by filtration of the radiation from fluorescent UV tubes. Mice were exposed to these radiation sources at doses systematically varying in UVB radiation content but supplying increasing proportions of UVA radiation. All radiation sources were found to generate approximately 35% cis -urocanic acid in the epidermis, thus normalizing the sources for cis -urocanic acid production. However, only those sources richest in short-wavelength UVB resulted in suppression of the systemic contact hypersensitivity response. These sources also induced the greatest erythema reaction, measured as its edema component, in the exposed skin. A strong correlation was thus demonstrated between the induction of edema and the suppression of contact hypersensitivity, but there appeared to be no correlation between the generation of epidermal cis-urocanic acid and suppression of contact hypersensitivity. The sources richest in UVA content did not result in suppression of contact hypersensitivity: furthermore mice previously irradiated with such UVA-rich sources were refractory to the immunosuppressive action of exogenous cis-urocanic acid. A protective effect of the increased UVA content thus appeared to be inhibiting immunosuppression by the available endogenously generated or exogenously applied cⁱs-urocanic acid.     

Interaction of UVB-absorbing sunscreen ingredients with cutaneous molecules may alter photoimmune protection.

Studies of the photoimmunoprotective properties of sunscreens have produced disparate results. In this study in hairless mice, we compared two UVB absorbers, 2-ethylhexyl-p-methoxycinnamate (2-EHMC) and octyl-N-dimethyl-p-aminobenzoate (o-PABA), individually formulated in a common base lotion with a sunburn protection factor of 6. We measured their capacity to protect against suppression of the contact hypersensitivity (CHS) induced by three daily exposures of the dorsum to 6x the minimal erythemal/edematous dose (MED) of solar-simulated UV radiation (SSUV), in comparison with base lotion-treated mice exposed to 3 x 1 MED of SSUV. All treatments produced a similar minimal erythema. CHS was equally suppressed in mice irradiated through o-PABA and base lotion, but the suppression was significantly reduced in mice irradiated through 2-EHMC. Neither UVB absorber inhibited the epidermal photoisomerization to the immunosuppressive mediator, cis-urocanic acid. However, when mice were treated with exogenous cis-urocanic acid topically on the dorsum, but not when injected subcutaneously on the abdomen, suppression of CHS was observed in o-PABA- and base lotion-treated mice, but not in 2-EHMC-treated mice. Thus, the enhanced immunoprotection in mice irradiated through 2-EHMC apparently resulted from the direct inactivation of epidermal cis-urocanic acid by 2-EHMC. We conclude that comparative assessment of photoimmunoprotection by UV absorbers requires SSUV, erythemally matched exposures and consideration of potential interactions with cutaneous molecules.     

Differential effects of UVA1 and UVB radiation on Langerhans cell migration in mice

The UVB (280-315 nm)- and UVA1 (340-400 nm)-induced migration of Langerhans cells (LC) from the epidermis and accumulation of dendritic cells (DC) in the lymph nodes draining the exposed skin site of C3H/HeN mice have been investigated. One minimum erythemal dose (MED) of UVB (1.5 kJ/m2) and of UVA1 (500 kJ/m2) were chosen, which have been shown previously to suppress delayed hypersensitivity (DTH). UVB irradiation resulted in a reduction in epidermal LC numbers, local to the site of the exposure, which was most apparent 12 h after exposure, but, in contrast, UVA1 had no significant effect even at 72 h after exposure. UVA1 did not exert any protection against the UVB-mediated depletion in LC numbers. The reduction in local LC following UVB exposure was prevented by systemic (intraperitoneal) treatment of mice with neutralising antibodies to either tumor necrosis factor (TNF)-alpha or interleukin (IL)-beta 2 h prior to the irradiation. It has been reported previously that UVB exposure caused an increase in the number of dendritic cells (DC) in the lymph nodes draining the irradiated skin site. In the present study we have shown that UVA1 had a similar effect. Pretreatment of the mice with neutralising antibodies to IL-1beta (by intraperitoneal injection) substantially inhibited DC accumulation induced by both UV regimens. However, anti-TNF-alpha antibodies affected only the UVB-induced increase, and did not alter the elevation in DC numbers observed following UVA1 exposure. These results indicate that UVB causes the migration of LC from the epidermis and an accumulation of DC in the draining lymph nodes by a mechanism that requires both TNF-alpha and IL-1beta. In contrast, UVAI does not cause LC migration from the epidermis and the accumulation of DC in the draining lymph nodes observed following UVA1 exposure requires IL-1beta, but not TNF-alpha. It is likely therefore that UVA1 acts through a different mechanism from UVB and may target a cutaneous antigen presenting cell other than LC, such as the dermal DC.     

Protection against photoaging in the hairless mouse by the isoflavone equol

Topical application of the isoflavone equol immediately following solar-simulated UV (SSUV) radiation exposure has previously been demonstrated to have significant photoprotective effects. Equol reduced both the inflammatory edema and the systemic suppression of the contact hypersensitivity reaction in hairless mice. Furthermore, daily topical equol application immediately following irradiation during a 10-week chronic SSUV exposure regime also reduced photocarcinogenesis severity in the mouse. This study examines the potential for topical equol to prevent photoaging in response to chronic SSUV irradiation for up to 30 weeks. We did not find consistent expression of the characteristic markers of photoaging until 30 weeks, although moderate epidermal hyperplasia and a transient increase in dermal mast cell numbers were evident after 1 week. Daily application of 10 muM equol lotion significantly reduced these early changes. However after 30 weeks of SSUV exposure, photoaging was well developed, as shown histologically by markedly increased epidermal hyperplasia, increased dermal mast cell number, pronounced focal elastotic deposits, degraded dermal collagen and deposition of glycosaminoglycans in the lower dermis. Topical equol treatment protected significantly from each of these impairments, as demonstrated histologically and quantitatively. Additionally, equol was found to have strong antioxidant action against acute UVA (320-400 nm)-induced lipid peroxidation of mouse skin, this property accounting for its antiphotoaging mechanism. The evidence for equol's antiphotoaging activity, taken together with its anti-inflammatory, immunoprotective and anticarcinogenic efficacy against SSUV irradiation in the mouse, suggests that equol could be developed as a helpful topical photoprotective agent for daily use by humans.     

ACTIVATION OF NF-KB IN HUMAN SKIN FIBROBLASTS BY THE OXIDATIVE STRESS GENERATED BY UVA RADIATION

We have examined the role of the nucleus and the membrane in the activation of nuclear factor (NF)-KB by oxidant stress generated via the UVA (320–380nm) component of solar radiation. Nuclear extracts from human skin fibroblasts that had been irradiated with UVA at doses that caused little DNA damage contained activated NF-KB that bound to its recognition sequence in DNA. The UVA radiation-dependent activation of NF-KB in enucleated cells confirmed that the nucleus was not involved. On the other hand, UVA radiation-dependent activation of NF-KB appeared to be correlated with membrane damage, and activation could be prevented by a-tocopherol and butylated hydroxytol-uene, agents that inhibited UVA radiation-dependent peroxidation of cell membrane lipids. The activation of NF-KB by the DNA damaging agents UVC (200–290nm) and UVB (290–320nm) radiation also only occurred at doses where significant membrane damage was induced, and, overall, activation was not correlated with the relative levels of DNA damage induced by UVC/UVB and UVA radiations. We conclude that the oxidative modification of membrane components may be an important factor to consider in the UV radiation-dependent activation of NF-KB over all wavelength ranges examined.     

Both solar UVA and UVB radiation impair conidial culturability and delay germination in the entomopathogenic fungus Metarhizium anisopliae.

The entomopathogenic hyphomycete Metarhizium anisopliae has been used in programs of agricultural pest and disease vector control in several countries. Exposure to simulated solar radiation for a few hours can completely inactivate the conidia of the fungus. In the present study we determined the effect of exposures to full-spectrum sunlight and to solar ultraviolet A radiation at 320-400 nm (UVA) on the conidial culturability and germination of three M. anisopliae strains. The exposures were performed in July and August 2000 in Logan, UT. The strains showed wide variation in tolerance when exposed to full-spectrum sunlight as well as to UVA sunlight. Four-hour exposures to full-spectrum sunlight reduced the relative culturability by approximately 30% for strain ARSEF 324 and by 100% for strains ARSEF 23 and 2575. The relative UV sensitivity of the two more sensitive strains was different under solar UV from that under ultraviolet B radiation at 280-320 nm (UVB) in the laboratory. Four-hour exposures to solar UVA reduced the relative culturability by 10% for strain ARSEF 324, 40% for strain ARSEF 23 and 60% for strain ARSEF 2575. Exposures to both full-spectrum sunlight and UVA sunlight delayed the germination of the surviving conidia of all three strains. These results, in addition to confirming the deleterious effects of UVB, clearly demonstrate the negative effects of UVA sunlight on the survival and germination of M. anisopliae conidia under natural conditions. The negative effects of UVA in sunlight also emphasize that the biological spectral weighting functions for this fungus must not neglect the UVA wavelengths.     

AN ACTION SPECTRUM FOR ULTRAVIOLET INDUCED ELASTOSIS IN HAIRLESS MICE: QUANTIFICATION OF ELASTOSIS BY IMAGE ANALYSIS

To determine an action spectrum for ultraviolet (UV)-induced elastosis, four groups of 24 albino hairless mice each were exposed to four different spectra emitted by a xenon arc solar simulator fitted with cut-off filters (Schott WG 320, 335, 345, and 360). These filters progressively removed more of the shorter wavelengths until, in the final spectrum, only long wavelength UVA (greater than 335 nm) remained. Exposures continued up to 62 weeks. A fifth group of mice served as controls. Skin biopsies were taken at pre-determined dose points and were processed for light microscopy. Elastosis was quantified by computerized image analysis, yielding dose-response curves for each spectrum. The total energy required for a 50% increase in elastic tissue compared to controls was determined graphically for each spectrum. These were: WG 320, 65 J/cm2; WG 335, 865 J/cm2; WG 345, 1230 J/cm2; and WG 360, 2000 J/cm2. Our results were tested against published action spectra for erythema, photocarcinogenesis and elastosis. The erythema spectrum was the most predictive for elastosis except that the longer UVA wavelengths were less effective for elastosis than for erythema. Solar simulating radiation (WG 320 filter) with its UVB component was the most effective in inducing elastosis. Full spectrum UVA (WG 345) required 20 times more energy while long wavelength UVA (WG 360) required 30 times more energy to induce equivalent elastosis.     

No adaptation to UV-induced immunosuppression and DNA damage following exposure of mice to chronic UV-exposure

It is well known that ultraviolet (UV) radiation induces erythema, immunosuppression and carcinogenesis. We hypothesized that chronic exposure to solar UV radiation induces adaptation that eventually prevents the suppression of acquired immunity. We studied adaptation for UV-induced immunosuppression after chronic exposure of mice to a suberythemal dose of solar simulated radiation (SSR) with Cleo Natural lamps, and subsequent exposure to an immunosuppressive dose of solar or UVB radiation (TL12). After UV dosing, the mice were sensitized and challenged with either diphenylcyclopropenone (DPCP) or picryl chloride (PCl). To assess the adaptation induced by solar simulated radiation, we measured the proliferative response and cytokine production of skin-draining lymph node cells after immunization to DPCP, the contact hypersensitivity (CHS) response to PCl, and thymine-thymine (T-T) cyclobutane dimers in the skin of mice. After induction of immunosuppression by SSR or by TL12 lamps, the proliferative response of draining lymph node cells after challenge with DPCP, or the CHS after challenge with PCl, showed significant suppression of the immune response. Chronic irradiation from SSR preceding the immunosuppressive dose of UV failed to restore the suppressed immune response. Reduced lipopolysaccharide-triggered cytokine production (of IL-12p40, IFN-gamma, IL-6 and TNF-alpha) by draining lymph node cells of mice sensitized and challenged with DPCP indicated that no adaptation is induced. In addition, the mice were not protected from T-T dimer DNA damage after chronic solar irradiation. Our studies reveal no evidence that chronic exposure to low doses of SSR induces adaptation to UV-induced suppression of acquired immunity.     

Measurement of UVA Exposure to Solar Radiation

Exposure to solar UVA (320–400 nm) radiation can damage DNA and lead to skin disorders. Conventional dosim-etry using a single piece of polysulfone or diglycol carbonate (CR-39) cannot provide accurate measurement of the biologically effective irradiance for erythema for the UVA waveband. A package employing four dosimeters (polysulfone, nalidixic acid, 8-methoxypsoralen and phe-nothiazine) has been shown to be effective for use as a spectrum evaluator for evaluating the UVA source spectrum. In Brisbane, on a horizontal position, the spectrum evaluator requires about 5 min exposure in summer and about 20 min in winter. This amounts to about 10 mJ cm-² of erythemal UV radiation.     

An Analysis of UVA Emissions from Sunlamps and the Potential Importance for Melanoma

Abstract— Exposure to solar UV radiation is a risk factor for cutaneous malignant melanoma (CMM). Epidemiologic studies have also considered the use of sunlamps as a possible contributor to CMM. We measured and analyzed the emission spectra of six different currently marketed sunlamps and a historical sunlamp, the UVB-emitting FS lamp, and compared the results to solar exposure. For a typical tanner (20 sessions @ 2 minimal erythema doses (MED)/session), the annual UVA doses from commonly used fluorescent sunlamps were 0.3-1.2 times that received from the sun. For a frequent tanner (100 sessions @ 4 MED/session), the annual UVA doses from fluorescent sunlamps were 1.2-4.7 times that received from the sun and 12 times for recently available, high-pressure sunlamps. To determine biologically effective doses, action spectra for squamous cell carcinoma (SCC) in humans and for melanoma in the Xiphophorus fish (XFM) were applied to the sunlamps' emission spectra. The results for the effective doses using the SCC action spectrum tracked the UVB doses, while the results using the XFM action spectrum tracked the UVA doses. When combined with UV exposure received from the sun, typical sunlamp use results in an approximate doubling of annual effective dose, if the XFM action spectrum is applied. Frequent use, however, can increase the annual effective XFM dose by as much as 6 times what would be received from the sun alone for fluorescent sunlamps and as much as 12 times for newer, high-pressure sunlamps.     

The Value of the Ratio of UVA to UVB in Sunlight

The objective of this communication is to present the calculated ratio between UVA and UVB irradiance from sunrise to sunset and under a number of weather conditions. UVA plays an important role in the sun spectrum and a lot of attention has been paid lately regarding the protection of people from UVA. Solar spectra were collected in Kuwait City located at 29.3^oNorth latitude (similar to that of Houston, TX) over a period of 8 months and under various weather conditions. Spectra were collected from 260 nm to 400 nm in 2 nm increments for solar elevation angles from 10^o to 90^o using a calibrated Optronics Laboratories OL‐742 Spectroradiometer. The measurements reported in this study the ratio of UVA (320–400 nm) to UVB (280–320 nm) in solar terrestrial radiation remains essentially constant and equal to 20 for the part of the day when the solar elevation is greater than 60^o. Consequently the value of the ratio of solar UVA/UVB should be considered as equal to 20 for studies in photobiology and photomedicine. When the wavelength limiting the range of UVA and UVB is 315 nm (i.e. UVB: 280–315 nm and UVA: 315–400 nm) the ratio of UVA to UVB becomes equal to 41.     

Comparative study of erythema response to UVA radiation in guinea pigs and humans

Abstract— Cutaneous erythema resulting from UVB radiation has been extensively studied in both humans and experimental animals; however, although there have been several investigations defining UVA erythema in humans, there have been no comprehensive reports using an animal model. Accordingly, studies were designed to assess UVA erythema in terms of time of onset; time of maximum reaction; and fluence-response relationships in albino guinea pigs and to compare these with similar studies in humans. Two high intensity Hg vapor lamps containing iron and gallium halides were used as UVA light sources. Both have sufficient fiuence rates (190 to 260 W m^?2) so as to allow convenient exposure times for delivery of UVA erythemogenic fluences. UVA fluences of 20 times 10⁴, 40 times 10⁴ and 60 times 10⁴ J m^?2 were administered to 58 humans and 51 Hartley-strain albino guinea pigs. Data obtained in humans indicate that UVA erythema develops immediately after irradiance with a maximum erythema peak occurring in 6 to 12 h and markedly diminishing by 24 h. The minimal fiuence required to elicit erythema responses in Type I and Type II individuals was found to be approximately 40 times 10⁴ J m^?2 of UVA when observed at 6 h, a fiuence about 1000 times greater than that used to elicit UVB erythema. Studies in 51 guinea pigs demonstrated erythema immediately after irradiance, with a peak between 8 to 12 h, and a marked decrease in 48 h. The fiuence of UVA required to elicit erythema was similar to that required in humans. The two different light sources provided comparable data per unit exposure and were essentially similar to a Xe lamp. These data from both humans and guinea pigs strongly support the concept that UVA erythema can be assayed in guinea pigs and correlated with humans.     

Sunscreen Protection Against Ultraviolet Radiation-induced Pyrimidine Dimers in Mouse Epidermal DNA

Pyrimidine dimers were measured in epidermal DNA of SKH:HRI mice following exposure to solar-simulated UV radiation (SSUV, 290–400 nm) or to UVA (320–400 nm). Mice were exposed to SSUV or UVA after topical application (2 mg/cm²) of vehicle, a UVB absorber (5% 2-ethylhexyl p-methoxycinnamate [2-EHMC]), or a broad-spectrum UVA absorber (5% Mexoryl®SX). The rates of induction of pyrimidine dimers in untreated animals were 5.4 ± 0.57 times 10^-4 (mean ± SEM) and 7.6 ± 0.95 times 10^-6 dimers per 10⁸ Da of epidermal DNA per J/m² of SSUV and UVA, respectively. Topical application of Mexoryl®SX reduced the rate of induction of pyrimidine dimers in SSUV-exposed animals to 4.7 ± 0.44 times 10^-5 dimers per 10⁸ Da per J/m² for a dimer induction protection factor (PF) of 11.5 (5.4 times 10 ⁴/4.7 times 10^-5). The rate of dimer induction in Mexoryl®SX-treated, UVA-ex-posed mice was 0.95 ± 0.2 times 10^-6 dimers per 10⁸ Da per J/m² (PF = 8.0). The 2-EHMC at a concentration of 5% (wt/wt) was significantly less effective than Mexoryl®SX in preventing the induction of pyrimidine dimers in animals exposed to either SSUV or UVA. The rates of dimer induction in 2-EHMC-treated mice were 8.2 ± 1.1 times 10^-5 and 3.8 ± 0.33 times 10^-6 dimers per Da per J/m² of SSUV (PF = 6.6) and UVA (PF = 2.0), respectively. Upon normalizing to the efficacy for edema induction, UVA induced approximately one-fourth the number of pyrimidine dimers per equivalent edematous response when compared to SSUV.     

PYRIMIDINE DIMER FORMATION IN HUMAN SKIN

Cyclobutyl pyrimidine dimers are major photoproducts formed upon irradiation of DNA with ultraviolet light. We have developed a method for detecting as few as one pyrimidine dimer per million bases in about 50 ng of non-radioactive DNA, and have used this method to quantitate dimer yields in human skin DNA exposed in situ to UV. We found that UVA radiation (320–400 nm) produces detectable levels of dimers in the DNA of human skin. We also measured UVB-induced dimer yields in skin of individuals of differing sun sensitivity and found higher yields in individuals with higher UVB minimal erythema doses and greater sun sensitivity. These approaches should provide important information on damage induced in human skin upon exposure to natural or artificial sources of ultraviolet radiation.     

Suppression of an established immune response by UVA--a critical role for mast cells

Exposing experimental animals or human volunteers to UVA II (320-340 nm) radiation after immunization suppresses immunologic memory and the elicitation of delayed-in-time hypersensitivity reactions. Previous studies indicated that the mechanisms underlying UVA-induced immune suppression are similar to those described for UVB-induced immune suppression, i.e. transferred by T regulatory cells, overcome by repairing DNA damage, neutralizing interleukin (IL)-10 activity, or injecting recombinant IL-12. Here we continued our examination of the mechanisms involved in UVA II-induced suppression. Antibodies to cis-urocanic acid blocked UVA-induced immune suppression. Treating UVA-irradiated mice with histamine receptor antagonists, calcitonin gene-related peptide (CGRP) receptor antagonists or platelet activating factor receptor antagonists blocked immune suppression in UVA-irradiated mice. In light of the fact that cis-urocanic acid and CGRP target mast cells, which can then release platelet activating factor and histamine, we measured UVA-induced immune suppression in mast cell-deficient mice. No immune suppression was noted in UVA-irradiated mast cell-deficient mice. These findings indicate that exposure to UVA II activates many of the same immune regulatory factors activated by UVB to induce immune suppression. Moreover, they indicate that mast cells play a critical role in UVA-induced suppression of secondary immune reactions.     

CARCINOGENIC and MELANOGENIC EFFECTS OF A FILTERED METAL HALIDE UVA SOURCE and A TUBULAR FLUORESCENT UVA TANNING SOURCE WITH OR WITHOUT ADDITIONAL SOLAR-SIMULATED UV RADIATION IN HAIRLESS MICE

Abstract— The carcinogenic and melanogenic effects of a filtered metal halide source (UVASUN) that emits UV radiation in a range from 340 to 400 nm and a bank of Philips TL 09R tubes (TL 09) emitting in a range from 310 to 400 nm were studied in lightly pigmented hairless hr/hr C3H/Tif mice. Both the carcinogenic effect of the two UVA radiation sources alone and in combination with a UV source, consisting of one Philips TL 12 and five Bellarium-S SA-1–12 tubes emitting radiation somewhat similar to the UV part of the solar spectrum (SOLAR UV), were investigated. Finally, the melanogenic effect of exposure to the two UVA sources were studied. The mice were exposed to the UVA sources 30 min/ day, 5 days/week, in equal erythemogenic doses, calculated by using the Commission Internationale de 1'Eclairage human erythema action spectrum. Equal erythemogenic doses of TL 09 and UVASUN induced the same degree of skin pigmentation, but skin tumor development was enhanced in mice exposed to TL 09 compared with UVASUN ( P < 0.0005). For all but one tumor, endpoint pretreatment with TL 09 or UVASUN for 91 days did not influence tumor development during subsequent exposure to SOLAR UV radiation 10 min/day, 4 days/week. Exposure to the two UVA radiation sources after 91 days of SOLAR UV exposure significantly enhanced skin tumor development. Overall, the data on the interaction between exposure to the UVA sources and SOLAR UV indicated that the risk of SOLAR UV-induced carcinogenesis was independent of the type of prior-UVA exposure and post-UVA exposure.