Protection against photodynamic therapy (PDT)-induced photosensitivity by fabric materials.

"Special" highly protective fabrics are now available that offer broad-spectrum protection in preventing sunburn, and possibly other types of photodamage. It is important to know to what extent these fabrics are capable of protecting the wearer against skin cancer, photosensitivity disorders, and inadvertent phototoxic reactions from photodynamic therapy (PDT). We assess the ability of one such special (Solumbra) fabric and one "typical" summer fabric to provide protection against PDT phototoxicity produced in tape-stripped Sk-1 hairless mice by topical 5-aminolevulinic acid (ALA) and (primarily) visible light (360-800 nm). Since ALA-derived photosensitizers absorb most of the visible spectrum, results from these studies give a good indication of the photoprotective capability of these fabrics throughout this region. Mice were irradiated dorsally with a Kodak slide projector equipped with a 300 W tungsten-halogen lamp (I0 = 48.3 mW/cm2). After determining the minimal phototoxic dose (MPD) to be 1.40 +/- 0.4 J/cm2, we irradiated the tape-stripped ALA-sensitized mice through the stretched test fabrics with appropriate multiples of the MPD. The special fabric provided protection against 25-30 MPD visible light between 360-800 nm in 14/14 mice. The typical fabric failed to provide protection against 2.5 MPD of the same spectrum. No phototoxic or other adverse responses were seen with either the ALA or light control. In conclusion, the Solumbra fabric is much more protective against ALA photosensitization than the typical fabric. Both appear better at blocking UV than visible light.

Photoprotection of mammalian acid-soluble collagen by cuttlefish sepia melanin in vitro.

Several important clinical conditions can result in close association between the pigment melanin and dermal collagen. Because melanin and its precursors can be chemically reactive in ground and excited states, it is important to know whether the resulting melanin-collagen interaction results in photoprotection or photoaggression. Acidic and neutral air-saturated collagen suspensions (0.033%) were irradiated with 0-2.6 x 10(4) J/m2 UVC or with 0-83 x 10(4) J/m2 solar-simulating UV radiation (SSR). Photochemical destruction of a photolabile collagen fluorophore (lambda em 360 nm) and collagen chain degradation were monitored as functions of irradiation time in the presence and absence of added (0-100 micrograms) sepia eumelanin. Melanin retarded collagen photodamage but did not qualitatively alter the fluorescence fading kinetics. Both H2O2 and O2-. can be produced by UV irradiation of eumelanin. Added H2O2 and KO2 destroyed collagen fluorescence and caused 50% chain degradation at ca 10-20-fold molar excess. Previous studies have demonstrated that eumelanins efficiently scavenge O2-.. We demonstrated that eumelanin also efficiently scavenges H2O2 as evidenced by its ability to (a) compete with scopoletin for peroxide uptake and (b) directly take up H2O2 through a dialysis bag. The latter observation suggests that peroxide scavenging could occur in vivo by melanin sequestered in melanophages. Thus, neither UV-generated O2-. nor H2O2 are likely to be present in concentrations high enough to cause measurable collagen damage. Absorption and/or scattering of excitation radiation away from the target chromophore appears to be the primary photoprotection mechanism, although scavenging of active O2 intermediates may play an important, if subtle role.

Protection against UV photocarcinogenesis by fabric materials.

BACKGROUND: Clothing fabrics have long been considered effective protection against short-term and long-term sun damage. Recently, special "highly UV-protective" fabrics have been developed specifically for photosensitive patients. OBJECTIVE: To determine if one such fabric will protect hairless mice against (pre)malignant lesions under conditions that will produce skin cancers through a typical summer fabric of moderate sun protection factor (SPF). METHODS: After prior determination of minimal erythemal dose, four sets of 10 animals were divided into the following groups: (A) dark control (no irradiation); (B) positive control (no fabric); (C) "typical summer" fabric (SPF = 6.5 +/- 1.0); and (D) "special" fabric (SPF > 30 across a broad spectrum). Mice were irradiated on the dorsal surface 5 days per week, with biweekly incremental increases (roughly 20% of the starting dose), for 12 weeks. Group B started at 6.3 J/cm2, with biweekly increases of 1.45 J/cm2 (total dose, 596 J/cm2); groups After irradiation, mice were observed for clinical and histologic signs of pre(malignant lesions for an additional 12 weeks. RESULTS: At the end of the 12-week irradiation period, nine mice in group B and six mice in group C had actinic keratosis-like lesions, whereas one mouse in group B and two mice in group C had squamous cell carcinoma. By week 24, all mice in groups B and C had squamous cell carcinoma. Mice in groups A and D showed no discernable reaction at any time. Biopsy specimens confirmed the clinical results. CONCLUSION: Typical summer clothing fabrics may offer inadequate protection against skin cancer and pose high risk to chronically photosensitive patients. The use of appropriate sun protective apparel should offer effective protection to photosensitive patients against short-term and long-term photodamage.

In vivo depigmentation by hydroxybenzene derivatives.

Certain mono- and dihydroxybenzene derivatives are selectively cytotoxic for melanocytes in vivo, and can cause depigmentation of skin and hair. We produced selective melanocytotoxicity/hair depigmentation in C57Bl mice by injection of 0.032-1.0% p-t-butylcatechol (tBC) or p-hydroxyanisole (MMEH) in physiological saline. No depigmentation occurred on injection of 3,4-dihydroxyphenylalanine (DOPA) or 3,4-dihydroxyphenylacetic acid (DOPAC). Light- and electron-microscopic examination of biopsy specimens taken from depigmented areas indicates selective melanocyte damage as early as 2 h post-injection. Melanocytes from anagen hair are most susceptible to depigmentation. All four compounds are substrates for tyrosinase, but only tBC and MMEH generate their respective isolable 1,2-benzoquinones, tBCQ and MMEHQ. These caused depigmentation in C57Bl mice to a comparable degree to the parent compounds. DOPA- and DOPAC-quinones (DOPAQ and DOPACQ) are not spectroscopically detectable in solution, suggesting extremely low steady-state levels of these compounds. The net observed rate of reaction of the respective 1,2-quinone with 300 microM bovine serum albumin (BSA) in vitro varies widely, with tBCQ >> MMEHQ = DOPACQ >> DOPAQ. The results are consistent with a mechanism involving attack of -SH on melanosomal proteins and/or enzymes by tyrosinase-generated 1,2-quinones. This mechanism evidently differs from that involved in in vitro hydroxybenzene melanocytotoxicity of melanoma cells, in which active oxygen intermediates generated by hydroxybenzene autoxidation play a significant role. The most reliable prognosticator of in vivo depigmentation appears to be the ability of the depigmenter to form a spectroscopically stable 1,2-quinone which is capable of reacting with protein -SH.

T4 cell receptor distortion in acquired immune deficiency syndrome.

Among the possible affects of the HIV virus on T-cells in Acquired Immune Deficiency Syndrome is the cell membrane distortion of the T4 cell protein receptor for Genetically Related Macrophage Factor (GRF). The integrity of this specific T-cell receptor takes on profound significance due to its relationship to soluble antigen. Alpha-tocopheral has been shown to assist in the maintenance of cell membrane structure and may have application in a strategy of membrane restoration. Adoptive Transfer, a method of immune cell alteration applicable in anti-tumor therapy, may play a role in the mechanics of such a strategy.