The Photobiology of UV Damage to Skin

A frequently recurring question within the Fluorescent Mineral Facebook Group is how UV affects the skin and eyes. At the annual NERF meeting In Nov 2013 an excellent talk and discussion on this topic was presented and documented by Howie Green. Below is a copy of Howie's writeup, published here with the author's permission. (First published in the FMS UV Waves, v44, n4)

Molecular biologist Dr. Daniel Yarosh threw out the first NERF ball at the 2013 meeting. I've been aware of Dan's work since he hosted my older son, Bryan, for summer research internships many years ago at his dermatology and skin care company, Applied Genetics Incorporated Dermatics. Dan's presence is a somewhat historic achievement for me, as I've been pursuing him as a speaker for many years, and his participation attendance brought Bryan out of the woodwork to attend his first FMS meeting. At the time of our meeting, Dan was the Senior Vice President of Basic Science Research at Estée Lauder and is now their Chief Technology Advisor, R&D. I would also suggest reading his excellent book The New Science of Perfect Skin. At our meeting, Dan described The Photobiology of UV Damage to Skin, an expanded discussion of which follows.

Dan began by illustrating the spectrum of light bombarding Earth from our sun, Sol. Ultraviolet light is the specialized designation for electromagnetic radiation with wavelengths between 100 nm and 400 nm. The energy of light is inversely proportional to its wavelength. A low-density band of ozone (O3) in the Earth's stratosphere acts as a filter absorbing higher energy UV light. Consequently, the wavelengths impinging on us include mostly UVA (320-400 nm), some UVB (280-320 nm), and a bit of UVC. Two effects of UV light, the induction of erythema (from the Greek erythros, a redness of the skin or mucous membranes, caused by dilation of superficial capillaries) and DNA damage, decay logarithmically as energy decreases (as wavelength increases) going from UVB to UVA exposure. The action spectra of these two biological endpoints overlap, leading to the obvious conclusion that both are a consequence of DNA damage. Sunburn, immunosupression of contact hypersensitivity, skin cancer, and premature aging of the skin (sun spots and collagen destruction leading to wrinkles and loss of elasticity) are other dermatologic effects of sunlight. Dan had an amazing slide of a career truck driver illustrating this phenomenon. The chronically sun-exposed left side of his face was dramatically more wrinkled than the right side.

The pathological effects on skin of UV are ALL linked to DNA damage. Sunburn is an acute effect targeting the skin and cornea, while a suntan is a delayed defense against further damage. There are two different mechanisms involved in induction of a tan by UV exposure. Oxidative stress caused by UVA exposure in turn oxidizes and rapidly darkens melanin, which is located in cells (melanocytes) of the epidermis and in the middle layer of the uvea of the eye. Melanin is the pigment primarily responsible for skin color, and ordinarily protects the skin by effectively absorbing UV light and converting it into small amounts of harmless heat. Because UVA causes melanin to be released from cells in which it is already stored, but doesn't increase melanin production (melanogenesis) significantly, this effect only cosmetic. However, without an increase in melanin production, there is little increase in protection against UVB, or protection against sunburn. In a second process, triggered primarily by UVB, there is an increase in production of melanin, which is the body's reaction to direct DNA damage from UV radiation. The tan that is created by increased melanin production, which first becomes visible about 72 hours after exposure, lasts much longer than that caused by the oxidation of existing melanin by UVA, and is actually theoretically protective against UV skin damage and sunburn, rather than being simply cosmetic. However, in order to cause true 'melanogenesis tanning' by means of UV exposure, some UVB- induced direct DNA damage must first occur.

The most serious delayed effect of UV light is skin cancer. Skin cancer is the most common form of cancer in the US, and one in five Americans will develop skin cancer in their lifetime. More than 3.5 million skin cancers in over two million people are diagnosed annually. Each cancer is designated according to the cell type from which it originates. Basal cell carcinoma, the most common skin cancer, is rarely fatal but can be disfiguring. Squamous cell carcinoma, the second most common type, is more dangerous. Melanoma, the rarest type, is cancer of the melanocytes in the skin or in the eye. Melanomas are aggressive, will spread by direct growth and metastasis, and are fatal if untreated. Of the seven most common cancers in the US, melanoma is the only one the incidence of which is increasing. Over 75.000 new cases of invasive melanoma are diagnosed annually in the US, and there are about 10,000 deaths each year from melanoma. (No statistics are available specifically for fluorescent mineral collectors.) Almost all basal cell and squamous cell cancers, and most melanomas, are a consequence of exposure to UV light from the sun. A person’s risk for melanoma doubles if he or she has had more than five sunburns in their past. The obvious interpretation is that there is no such thing as a protective pre-suntan, safe exposure in a tanning salon (97% UVA and 3% UVB), or a 'harmless' dorm room wall poster light turning Jimi Hendrix psychedelic.

There are healthy effects of UV light on skin. For example, photons of UVB, especially 295-297 nm, catalyze the synthesis of vitamin D3 from cholesterol in skin. This accounts for about 90% of our vitamin D requirement, most of the rest coming from dietary absorption from irradiated milk and cold water fish. Interestingly, there is also some speculation that endorphin release accompanying sun tanning results in an 'addiction-like' pleasurable sense of well-being.

To understand the mechanism of DNA damage and repair, a biochemistry primer is helpful. Our genes are comprised of DNA (deoxyribonucleic acid), which encodes the genetic instructions for the cellular functioning. Most DNA molecules consist of two biopolymer strands coiled around each other in a structure described as a double helix. Each DNA strand is comprised of four types of nucleotides, each made of a nitrogen-containing nucleobase, a sugar (deoxyribose), and a phosphate group. The nucleotide monomers are joined to each other by covalent phosphodiester bonds between the sugar of one nucleotide and the phosphate of the next, and form the outer backbone of the double helix. The nucleobase of each nucleotide is either a purine (adenine or guanine) or a pyrimidine (thymine or cytosine) (abbreviated A, G, T, or C.) The nucleobases of each polynucleotide strand point toward the inside of the molecule, and are joined to a nucleobase of the opposite polynucleotide strand by relatively weak hydrogen bonds, forming the double-stranded DNA helix. The nucleobase pairs are stacked like rungs of a ladder. Only certain neucleobases in the double helix are compatible with each other; normally A only pairs with T and C only pairs with G. This specificity of base pairing results in both strands being complimentary, each the predictable counterpart of the other.

The DNA that makes up the human genome can be subdivided into information bytes called genes. The human genome contains about 21,000 genes. Each gene encodes a unique protein that performs a specialized function in the cell. Unlike the sugar-phosphate backbone, the sequence of nucleobase pairs is unique for each gene, the 'meaning' of which is encoded in the specific sequence of the four bases. Since genes are hundreds to thousands of nucleotides long, the variety of possible base pair sequences is virtually unlimited. Cells use the two-step process of transcription and translation to read each gene and produce the string of amino acids that makes up a protein. The basic rules for translating a gene into a protein are laid out in the Universal Genetic Code. This is the sequence of nucleotides in DNA that serves as instructions for synthesizing proteins. The genetic code is based on an 'alphabet' consisting of sixty four triplets of nucleobases called codons. The order in which codons are strung together determines the order in which the amino acids for which they code are arranged in a protein.

In order for an organism to grow, cell division must take place. When a cell divides the daughter cells must have the same genetic information as the parent cell. Each parent molecule is comprised of two complimentary strands of DNA. This feature of DNA enables the precise copying of genes necessary for inheritance. During replication the two strands separate like a zipper, and because of the base-pairing rules, each original strand serves a template that determines the order of nucleotides which plug in to form the 'new' complimentary UV Waves July-August 2014 4 strand. After replicating, each new DNA molecule consists of one original strand and one new strand, and is identical to the parent molecule.

Please spend a few minutes watching the animations of all of these genetic topics on the website of the DNA Learning Center of the Cold Spring Harbor Laboratory. Go to http://www.dnalc.org/resources/3d/index.html.

The mechanism by which UV light causes DNA damage begins with the absorption of a photon of UV light by its chromophore. A chromophore is defined as the part of a molecule which absorbs certain wavelengths of light and transmits or reflects others, determining various optical properties such as color. The chromophore can be thought of as being analogous to the activator of fluorescence in minerals. The physical chemistry of the activators is central to our scientific study of fluorescent minerals. For example, the NERF meeting of 2012 included a presentation exploring the relationship between the structure and chemistry of activator systems in apatite group minerals and their fluorescent properties. A second talk described how UV light is absorbed by diamonds at defects called luminescence centers, causing fluorescence that is an identifying characteristic of different diamond types, as well as an aid in the detection of synthetic diamonds. As will be discussed later, our current meeting included a discussion of a special example of the interaction of UV light and an activator system, namely the phenomenon of tenebrescence in sodalite and tugtupite. Presentations in prior NERF meetings have also extended the analogy to biological systems. We've studied how various wavelengths light are absorbed by the chromophore of retinal opsin proteins, and subsequent mechanisms of signal transduction which result in color vision and in mood regulation (UV light has no mood regulatory effects). In past years, presentations have defined how UV and blue light are absorbed by light-sensitive fluorescent proteins in sea animals, the chromophores of which are structurally similar to opsin proteins, and which then undergo similar conformational chemical changes. We have studied the bioluminescence and biofluorescence of various fluorescent proteins in marine animals, and of one specific protein, green fluorescent protein (GFP). GFP has had a dramatic enough effect on medical science to have earned its discoverers the Nobel Prize in Chemistry in 2008.

The C=C double bonds of the aromatic ring structure of the nitrogenous DNA nucleobases, especially the pyrimidine bases, absorb UV light in the range of 260 nm most efficiently. There is little UV light of this wavelength in the ordinary sunlight that reaches our troposphere, but DNA can absorb UVB well also. As a molecule of DNA absorbs UVB, it does so by adding the energy at that wavelength to the vibrational energy of the molecule at a particular bond. When the vibration at that bond is already occurring at that wavelength or a harmonic of it, it absorbs the energy and begins to vibrate more strongly. The atoms on either end of the bond get farther apart as a result of the stronger vibration. With greater separation, the bond is more easily broken, allowing for a reaction with neighboring bases. If the neighboring base on the same strand is another pyrimidine, the UV-modified base forms a direct covalent bond with it instead of with the corresponding base on the complimentary strand.

The result of this cross-linking is an abnormal, tight four-carbon cyclobutane ring, the most commonly formed type being between two neighboring thymine bases. In many instances replication can proceed correctly in spite of this mutation. However, since there are four possible nucleobases, normal base pairing occurs with a chance frequency of only 1 in 4, and replication is frequently arrested. It is estimated that 50-100 DNA-damaging reactions occur during every second of exposure to sunlight. This direct DNA damage caused by UVB is the primary cause of melanoma in humans, but more frequently causes sunburn, basal cell cancer, and squamous cell cancer.

Indirect DNA damage occurs when a photon, usually UVA, is absorbed in the human skin by a UV Waves July-August 2014 5 chromophore that does not have the ability to convert the energy into harmless heat very quickly. Several natural molecules perform this internal conversion very quickly, reducing the unstable excited-state lifetime of the chromophore. This can be a crucial property for enabling photoprotection by molecules such as melanin, which has an internal conversion rate (a few femtoseconds, 10−15s) that is many orders of magnitude faster than an unstable UV-excited chromophore, or any man-made molecule for that matter. Molecules that have a long-lived excited state have a high probability for reaction with other molecules, generating dangerous free radicals and reactive oxygen species (ROS). These unstable chemical species can reach and react with intact DNA throughout the body by diffusion, causing oxidative damage to the DNA of any organ (unlike direct DNA damage, which affects only areas directly exposed to UVB light). That indirect DNA damage can occur remotely is indicated by the fact that malignant melanoma can be found in places that are not directly illuminated by the sun, in contrast to basal cell carcinoma and squamous cell carcinoma, which appear only on directly exposed locations on the body. Free radicals and ROS can cause damage to proteins, DNA, and cell membranes, 'scavenging' their electrons by oxidation, in turn causing a chain reaction of further oxidative damage. It is important to note that indirect DNA damage does not result in any clinically apparent warning signal or pain, like a sunburn.