Monday 31 May 2004
Solar radiation spans the spectrum of wavelengths between 200 and 4000 nm, including ultraviolet, visible, and infrared radiation. Ultraviolet radiation is divided into ultraviolet A (UVA), ultraviolet B (UVB), and ultraviolet C (UVC); 3% to 5% of the total solar radiation that penetrates the earth’s surface is ultraviolet radiation.
Ultraviolet (UV) radiation is electromagnetic radiation of a wavelength shorter than that of the visible region, but longer than that of soft X-rays. It can be subdivided into near UV (380-200 nm wavelength), far or vacuum UV (200-10 nm; abbrev. FUV or VUV), and extreme UV (1-31 nm; abbrev. EUV or XUV).
UVA light is also known as "dark-light" and, because of its longer wavelength, can penetrate most windows. It also penetrates deeper into the skin than UVB light and is thought to be a prime cause of wrinkles.
The acute effects of UVA and UVB are short-lived and reversible. They include erythema, pigmentation, and injury to Langerhans cells and keratinocytes in the epidermis. The kinetics and chemical mediators of these reactions differ in response to UVA and UVB.
Depending on the intensity and length of exposure, erythema, edema, and acute inflammation are mediated by release of histamine from mast cells in the dermis, synthesis of arachidonic acid metabolites, and the production of pro-inflammatory cytokines like IL-1.
UVA produces oxidation of melanin with transient, immediate darkening, especially in individuals with darker skin. Tanning induced by UVA and UVB is due to a delayed increase in the number of melanocytes, elongation and extension of dendritic processes, and transfer of melanin to keratinocytes. Tanning induced by UVB is protective against subsequent exposures; tanning induced by UVA provides limited protection. Both UVA and UVB deplete Langerhans cells and thus reduce the processing of antigens introduced through the epidermis. UVB causes apoptosis of keratinocytes in the epidermis, resulting in dyskeratotic, sunburn cells.
Repeated exposures to ultraviolet radiation
Repeated exposures to ultraviolet radiation give rise to changes in the skin that are characteristic of premature aging (e.g., wrinkling, solar elastosis, and irregularities in pigmentation).
In contrast to ionizing radiation that increases deposition of collagen in the dermis, ultraviolet radiation causes degenerative changes in elastin and collagen, leading to wrinkling, increased laxity, and a leathery appearance. These connective tissue alterations accumulate over time and are largely irreversible. They are caused by increased expression of the elastin gene, increased expression of matrix metalloproteinases that degrade collagen, and induction of a tissue inhibitor of matrix metalloproteinase.
Ozone in the atmosphere is an important protective agent against ultraviolet radiation because it completely absorbs all UVC and partially absorbs UVB.
Chlorofluorocarbons, used commercially as propellants, as solvents, and in refrigerators and air conditioners, interact with and deplete ozone. Such depletion is predicted to contribute to an increase in UVB and possibly UVC exposure, thus triggering a 2% to 4% increase in the incidence of skin cancers.
Some protection from the effects of UV light is afforded by window glasses: they absorb UVB radiation, but they transmit UVA radiation. Sunblocks and sunscreens offer greater protection because they absorb or block UVB and UVA to variable degrees. There are two major health effects of ultraviolet radiation: premature aging of the skin and skin cancer.
Skin damage by UVB
Skin damage induced by UVB is believed to be caused by the generation of reactive oxygen species and by damage to endogenous chromophores such as melanin. Ultraviolet radiation also damages DNA, resulting in the formation of pyrimidine dimers between adjacent pyrimidines on the same DNA strand. Other forms of DNA damage, for example, formation of pyrimidine-pyrimidone (6-4) photoproducts, single-stranded breaks, and DNA-protein cross-links, are also noted.
A unique spectrum of mutations has been identified in premalignant and malignant skin lesions in humans, involving adjacent pyrimidine bases in p53: C→T or CC→TT double-base substitutions. This observation provides strong evidence for an etiologic role of ultraviolet light in induction of skin cancer.
Exposure to UV radiation induces a series of molecular changes collectively referred to as the ultraviolet response pathway. The triggering of this pathway involves activation of RAS signalling with activation of mitogenactivated protein kinases and induction of cellular protooncogenes and other genes involved in cell proliferation. This effect is believed to be independent of DNA damage.
Subsequently, thymidine dinucleotides produced by ultraviolet radiation activate the p53 pathway in a manner analogous to DNA breaks produced by ionizing radiation. Thus, exposure to ultraviolet radiation can induce a protective cellular response leading to DNA repair, cell-cycle arrest, or apoptosis, depending on the intensity of exposure and the sensitivity of the target cell. The importance of DNA repair as a defense mechanism against skin cancer is illustrated by increased susceptibility of patients with xeroderma pigmentosum to ultraviolet light-induced skin cancers.
In skin, UVA, UVB and UVC can all damage collagen fibers and thereby accelerate aging of the skin. In general, UVA is the least harmful, but can contribute to the aging of skin, DNA damage and possibly skin cancer. It penetrates deeply and does not cause sunburn. Because it does not cause reddening of the skin (erythema) it cannot be measured in the SPF testing. There is no good clinical measurement of the blocking of UVA radiation, but it is important that sunscreen block both UVA and UVB.
UVB and cancer
UVB light can cause skin cancer. The UV radiation excites DNA molecules in skin cells, causing covalent bonds to form between adjacent thymine bases, producing thymidine dimers. Thymidine dimers do not base pair normally, which can cause distortion of the DNA helix, stalled replication, gaps, and misincorporation. These can lead to mutations, which can result in cancerous growths. The mutagenicity of UV radiation can be easily observed in bacteria cultures.
As with other carcinogens, UVB also causes mutations in oncogenes and tumor suppressor genes. In particular, mutant forms of the RAS and p53 genes have been detected both in human skin cancers and in UVB-induced cancers in mice. These mutations occur mainly at dipyrimidine sequences within the DNA, thus implicating UVB-induced genetic damage in the causation of skin cancers. In animal models, p53 mutations occur early after exposure to UVB, before the appearance of tumors.
As a defense against UV radiation, the body tans when exposed to moderate (depending on skin type) levels of radiation by releasing the brown pigment melanin. This helps to block UV penetration and prevent damage to the vulnerable skin tissues deeper down. Suntan lotion that partly blocks UV is widely available (often referred to as "sun block" or "sunscreen"). Most of these products contain an "SPF rating" that describes the amount of protection given. This protection applies only to UVB light. In any case, most dermatologists recommend against prolonged sunbathing.
UV toxicity on eyes
High intensities of UVB light are hazardous to the eyes, and exposure can cause welder flash (photokeratitis or arc eye) and may lead to cataracts, pterygium, and pinguecula formation.
Protective eyewear is beneficial to those who are working with or those who might be exposed to ultraviolet radiation, particularly short wave UV. Given that light may reach the eye from the sides, full coverage eye protection is usually warranted if there is an increased risk of exposure as in high altitude mountaineering. Mountaineers are exposed to higher than ordinary levels of UV radiation, both because there is less atmospheric filtering and because of reflection from snow and ice.
UV and immune system
A positive effect of UV light is that it induces the production of vitamin D in the skin. Grant (2002) claims tens of thousands of premature deaths occur in the US annually from cancer due to insufficient UVB exposures (apparently via vitamin D deficiency). Another effect of vitamin D deficiency is osteomalacia, which can result in bone pain, difficulty in weight bearing and sometimes fractures.
Ultraviolet radiation has other medical applications, in the treatment of skin conditions such as psoriasis. UVB and UVA radiation can be used, in conjunction with psoralens (PUVA treatment). Most effective in case of psoriasis is UV light with wavelength of 311 nm.
UV rays have a number of effects on cells, including inhibition of cell division, inactivation of enzymes, induction of mutations and, in sufficient dosage, death of cells. The carcinogenicity of UVB light is attributed to its formation of pyrimidine dimers in DNA.
This type of DNA damage is repaired by the nucleotide excision repair (NER) pathway. There are five steps in NER: (1) recognition of the DNA lesion, (2) incision of the damaged strand on both sites of the lesion, (3) removal of the damaged nucleotide, (4) synthesis of a nucleotide patch, and (5) its ligation.
In mammalian cells, the process may involve 30 or more proteins. It is postulated that with excessive sun exposure, the capacity of the NER pathway is overwhelmed; hence, some DNA damage remains unrepaired. This leads to large transcriptional errors and, in some instances, cancer.
The importance of the NER pathway of DNA repair is most graphically illustrated by a study of patients with the hereditary disorder xeroderma pigmentosum. This autosomal recessive disorder is characterized by extreme photosensitivity, a 2000-fold increased risk of skin cancer in sun-exposed skin and, in some cases, neurologic abnormalities.
The molecular basis of the degenerative changes in sun-exposed skin and occurrence of cutaneous tumors rests on an inherited inability to repair UV-induced DNA damage. Xeroderma pigmentosum is a genetically heterogeneous condition, with at least seven different variants. Each of these is caused by a mutation in one of several genes involved in NER.