Photocarcinogen

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A photocarcinogen is a substance which causes cancer when an organism is exposed to it, then illuminated. Many chemicals that are not carcinogenic can be photocarcinogenic when combined with exposure to light, especially UV. This can easily be understood from a photochemical perspective: The reactivity of a chemical substance itself might be low, but after illumination it transitions to an excited state, which is chemically much more reactive and therefore potentially harmful to biological tissue and DNA. Light can also split photocarcinogens, releasing free radicals, whose unpaired electrons cause them to be extremely reactive.

The type of UV radiation determines the characteristics of photocarcinogenesis. For example, UVA radiation characteristically gives rise to reactive oxygen species (ROS) such as hydrogen peroxide whereas UVB radiation correlates with CPD lesions. [1] The ROS are produced when endogenous photosensitizers are stimulated by UVA radiation. [1] DNA absorption of UV radiation primarily leads to CPD and 6-4 lesions. The neighboring pyrimidines form a cyclobutane pyrimidine dimer in a CPD lesion. DNA absorption of UV radiation can also lead to TC, CC, and TT lesions but with much less frequency. The failure of DNA repair mechanisms to fix such lesions notably characterizes photocarcinogenesis. [2]

In addition, UV radiation often increases the production of cytokines such as interleukin-10 which indirectly hinder antigen presentation in cells. Moreover, UV radiation frequently leads to mutations in the tumor suppressor gene p53 in photocarcinogenesis. [3]

Determination of photocarcinogenicity can be accomplished using different techniques, including epidemiological studies and in-vivo studies. In one in-vivo technique, hairless mice are exposed to suspected photocarcinogens, and are then exposed to different wavelengths of light, ranging from visible to UV-B. [4] Tumor incidence is compared to control mice that have not been exposed to the drug or chemical being tested.

Melanin is not a photocarcinogen, because it dissipates the excitation energy into small amounts of heat (see photoprotection). Oxybenzone (a component of some sunscreens) is suspected owing to its skin penetrating qualities and its production of free radicals. One medication that has been proven to be photocarcinogenic is psoralen. This drug is used in photodynamic therapy for many inflammatory skin conditions, where the drug is combined with skin exposure to UV light. Epidemiological studies dating back to the 1970s have shown a strong association between psoralen treatment and skin cancer incidence 5 to 15 years afterwards. [5] A logistic regression study has shown that there is a positive association between citrus consumption, both in the form of fruit and fruit juice, and risk of developing melanoma. This increased risk is most profound in fair-skinned individuals. The reason for this correlation is the high concentration of the photocarcinogenic compound psoralen in citrus fruits. [6]

See also

Related Research Articles

<span class="mw-page-title-main">Ultraviolet</span> Energetic, invisible radiant energy range

Ultraviolet radiation, also known as simply UV, is electromagnetic radiation of wavelengths of 10–400 nanometers, shorter than that of visible light, but longer than X-rays. UV radiation is present in sunlight, and constitutes about 10% of the total electromagnetic radiation output from the Sun. It is also produced by electric arcs, Cherenkov radiation, and specialized lights, such as mercury-vapor lamps, tanning lamps, and black lights.

<span class="mw-page-title-main">Skin cancer</span> Medical condition involving uncontrolled growth of skin cells

Skin cancers are cancers that arise from the skin. They are due to the development of abnormal cells that have the ability to invade or spread to other parts of the body. It occurs when skin cells grow uncontrollably, forming malignant tumors. The primary cause of skin cancer is prolonged exposure to ultraviolet (UV) radiation from the sun or tanning devices. Skin cancer is the most commonly diagnosed form of cancer in humans. There are three main types of skin cancers: basal-cell skin cancer (BCC), squamous-cell skin cancer (SCC) and melanoma. The first two, along with a number of less common skin cancers, are known as nonmelanoma skin cancer (NMSC). Basal-cell cancer grows slowly and can damage the tissue around it but is unlikely to spread to distant areas or result in death. It often appears as a painless raised area of skin that may be shiny with small blood vessels running over it or may present as a raised area with an ulcer. Squamous-cell skin cancer is more likely to spread. It usually presents as a hard lump with a scaly top but may also form an ulcer. Melanomas are the most aggressive. Signs include a mole that has changed in size, shape, color, has irregular edges, has more than one color, is itchy or bleeds.

<span class="mw-page-title-main">Photodynamic therapy</span> Form of phototherapy

Photodynamic therapy (PDT) is a form of phototherapy involving light and a photosensitizing chemical substance used in conjunction with molecular oxygen to elicit cell death (phototoxicity).

<span class="mw-page-title-main">Sun tanning</span> Darkening of skin in response to ultraviolet light

Sun tanning or tanning is the process whereby skin color is darkened or tanned. It is most often a result of exposure to ultraviolet (UV) radiation from sunlight or from artificial sources, such as a tanning lamp found in indoor tanning beds. People who deliberately tan their skin by exposure to the sun engage in a passive recreational activity of sun bathing. Some people use chemical products that can produce a tanning effect without exposure to ultraviolet radiation, known as sunless tanning.

<span class="mw-page-title-main">Indoor tanning</span> Tanning using an artificial source of ultraviolet light

Indoor tanning involves using a device that emits ultraviolet radiation to produce a cosmetic tan. Typically found in tanning salons, gyms, spas, hotels, and sporting facilities, and less often in private residences, the most common device is a horizontal tanning bed, also known as a sunbed or solarium. Vertical devices are known as tanning booths or stand-up sunbeds.

<span class="mw-page-title-main">Light therapy</span> Therapy involving intentional exposure to sunlight

Light therapy, also called phototherapy or bright light therapy is the exposure to direct sunlight or artificial light at controlled wavelengths in order to treat a variety of medical disorders, including seasonal affective disorder (SAD), circadian rhythm sleep-wake disorders, cancers, and skin wound infections. Treating skin conditions such as neurodermatitis, psoriasis, acne vulgaris, and eczema with ultraviolet light is called ultraviolet light therapy.

<span class="mw-page-title-main">Actinic keratosis</span> Rough skin induced by UV exposure

Actinic keratosis (AK), sometimes called solar keratosis or senile keratosis, is a pre-cancerous area of thick, scaly, or crusty skin. Actinic keratosis is a disorder of epidermal keratinocytes that is induced by ultraviolet (UV) light exposure.

PUVA is an ultraviolet light therapy treatment for skin diseases: vitiligo, eczema, psoriasis, graft-versus-host disease, mycosis fungoides, large plaque parapsoriasis, and cutaneous T-cell lymphoma, using the sensitizing effects of the drug psoralen. The psoralen is applied or taken orally to sensitize the skin, then the skin is exposed to UVA.

<span class="mw-page-title-main">Psoralen</span> Chemical compound

Psoralen is the parent compound in a family of naturally occurring organic compounds known as the linear furanocoumarins. It is structurally related to coumarin by the addition of a fused furan ring, and may be considered as a derivative of umbelliferone. Psoralen occurs naturally in the seeds of Psoralea corylifolia, as well as in the common fig, celery, parsley, West Indian satinwood, and in all citrus fruits. It is widely used in PUVA treatment for psoriasis, eczema, vitiligo, and cutaneous T-cell lymphoma; these applications are typically through the use of medications such as Methoxsalen. Many furanocoumarins are extremely toxic to fish, and some are deposited in streams in Indonesia to catch fish.

<span class="mw-page-title-main">Pyrimidine dimer</span> Type of damage to DNA

Pyrimidine dimers represent molecular lesions originating from thymine or cytosine bases within DNA, resulting from photochemical reactions. These lesions, commonly linked to direct DNA damage, are induced by ultraviolet light (UV), particularly UVC, result in the formation of covalent bonds between adjacent nitrogenous bases along the nucleotide chain near their carbon–carbon double bonds, the photo-coupled dimers are fluorescent. Such dimerization, which can also occur in double-stranded RNA (dsRNA) involving uracil or cytosine, leads to the creation of cyclobutane pyrimidine dimers (CPDs) and 6–4 photoproducts. These pre-mutagenic lesions modify the DNA helix structure, resulting in abnormal non-canonical base pairing and, consequently, adjacent thymines or cytosines in DNA will form a cyclobutane ring when joined together and cause a distortion in the DNA. This distortion prevents DNA replication and transcription mechanisms beyond the dimerization site.

Postreplication repair is the repair of damage to the DNA that takes place after replication.

<span class="mw-page-title-main">Trioxsalen</span> Chemical compound

Trioxsalen (trimethylpsoralen (TMP), trioxysalen (INN) or Trisoralen) is a furanocoumarin and a psoralen derivative. It is obtained from several plants, mainly Psoralea corylifolia. Like other psoralens it causes photosensitization of the skin. It is administered either topically or orally in conjunction with UV-A (the least damaging form of ultraviolet light) for phototherapy treatment of vitiligo and hand eczema. After photoactivation it creates interstrand cross-links in DNA, which can cause programmed cell death unless repaired by cellular mechanisms. In research it can be conjugated to dyes for confocal microscopy and used to visualize sites of DNA damage. The compound is also being explored for development of antisense oligonucleotides that can be cross-linked specifically to a mutant mRNA sequence without affecting normal transcripts differing at even a single base pair.

Tanning activators are chemicals that increase the effect of UV-radiation on the human skin.

<span class="mw-page-title-main">Phytophotodermatitis</span> Medical condition

Phytophotodermatitis, also known as berloque dermatitis, margarita photodermatitis, lime disease or lime phytodermatitis is a cutaneous phototoxic inflammatory reaction resulting from contact with a light-sensitizing botanical agent followed by exposure to ultraviolet A (UV-A) light. Symptoms include erythema, edema, blisters, and delayed hyperpigmentation. Heat and moisture tend to exacerbate the reaction.

<span class="mw-page-title-main">Bergapten</span> Chemical compound

Bergapten (5-methoxypsoralen) is a naturally-occurring organic chemical compound produced by numerous plant species, especially from the carrot family Apiaceae and the citrus family Rutaceae. For example, bergapten has been extracted from 24 species of the genus Heracleum in the family Apiaceae. In the family Rutaceae, various Citrus species contain significant amounts of bergapten, especially the bergamot orange, the micrantha, and certain varieties of lime and bitter orange.

<span class="mw-page-title-main">Sunburn</span> Burning of the skin by the suns radiation

Sunburn is a form of radiation burn that affects living tissue, such as skin, that results from an overexposure to ultraviolet (UV) radiation, usually from the Sun. Common symptoms in humans and other animals include red or reddish skin that is hot to the touch or painful, general fatigue, and mild dizziness. Other symptoms include blistering, peeling skin, swelling, itching, and nausea. Excessive UV radiation is the leading cause of (primarily) non-malignant skin tumors, which in extreme cases can be life-threatening. Sunburn is an inflammatory response in the tissue triggered by direct DNA damage by UV radiation. When the cells' DNA is overly damaged by UV radiation, type I cell-death is triggered and the tissue is replaced.

<span class="mw-page-title-main">Photoaging</span> Ultraviolet light-induced biological development over time

Photoaging or photoageing is a term used for the characteristic changes to skin induced by chronic UVA and UVB exposure. Tretinoin is the best studied retinoid in the treatment of photoaging.

Animal-type melanoma is a rare subtype of melanoma that is characterized by heavily pigmented dermal epithelioid and spindled melanocytes. Animal-type melanoma is also known to be called equine-type melanoma, pigment synthesizing melanoma, and pigmented epithelioid melanocytoma (PEM). While melanoma is known as the most aggressive skin cancer, the mortality for PEM is lower than in other melanoma types. Animal-type melanoma earned its name due to the resemblance of melanocytic tumors in grey horses.

<span class="mw-page-title-main">Angelicin</span> Chemical compound

Angelicin is the parent compound in a family of naturally occurring organic compounds known as the angular furanocoumarins. Structurally, it can be considered as benzapyra-2-one fused with a furan moiety in the 7,8-position. Angelicin is commonly found in certain Apiaceae and Fabaceae plant species such as Bituminaria bituminosa. It has a skin permeability coefficient (LogKp) of -2.46. The maximum absorption is observed at 300 nm. The 1HNMR spectrum is available; the infrared and mass spectra of angelicin can be found in this database. The sublimation of angelicin occurs at 120 °C and the pressure of 0.13 Pa. Angelicin is a coumarin.

<span class="mw-page-title-main">Light-emitting diode therapy</span>

Light-emitting diode therapy (LEDT) is a clinical approach that applies different wavelengths of light to cure diseases or conditions with skin-safe lights. Following NASA's innovation in the 1990s with Light Emitting Diodes (LEDs) that emit a specific narrow light spectrum, LED Therapy (LEDT) showed significant potential. The high precision of narrow-band LED therapy enabled its first use in clinical practices. The commonly used lights in LEDT are blue, red, green, yellow, and infrared (IR).

References

  1. 1 2 Bissonnette, Robert; Claveau, Joel; Gupta, Aditya K. (2006). "Ultraviolet a Radiation and The Need for Protection". Journal of Cutaneous Medicine and Surgery. 10 (3_suppl): S1–S7. doi:10.2310/7750.2006.00025. ISSN   1203-4754. S2CID   72445839.
  2. ↑ Black, H.S.; deGruijl, F.R.; Forbes, P.D.; Cleaver, J.E.; Ananthaswamy, H.N.; deFabo, E.C.; Ullrich, S.E.; Tyrrell, R.M. (August 1997). "Photocarcinogenesis: an overview". Journal of Photochemistry and Photobiology B: Biology. 40 (1): 29–47. doi:10.1016/S1011-1344(97)00021-3. PMID   9301042.
  3. ↑ Valejo Coelho, Margarida Moura; Matos, Tiago R.; Apetato, Margarida (September 2016). "The dark side of the light: mechanisms of photocarcinogenesis". Clinics in Dermatology. 34 (5): 563–570. doi:10.1016/j.clindermatol.2016.05.022. hdl: 10400.17/2717 . PMID   27638434.
  4. ↑ "National Toxicology Program: Fact Sheet" (PDF). 2006.
  5. ↑ O'Gorman, Susan M.; Murphy, Gillian M. (1 November 2013). "Photosensitizing Medications and Photocarcinogenesis". Photodermatology, Photoimmunology & Photomedicine. 30 (1): 8–14. doi: 10.1111/phpp.12085 . PMID   24393207.
  6. ↑ Marley, A.R.; Li, M.; Champion, V.L.; Song, Y.; Han, J.; Li, X. (2021). "The association between citrus consumption and melanoma risk in the UK Biobank*". British Journal of Dermatology. 185 (2): 353–362. doi:10.1111/bjd.19896. ISSN   0007-0963. PMC   8373643 . PMID   33782946.
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