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]

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Ultraviolet Form of electromagnetic radiation

Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nm to 400 nm (750 THz), 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 and specialized lights, such as mercury-vapor lamps, tanning lamps, and black lights. Although long-wavelength ultraviolet is not considered an ionizing radiation because its photons lack the energy to ionize atoms, it can cause chemical reactions and causes many substances to glow or fluoresce. Consequently, the chemical and biological effects of UV are greater than simple heating effects, and many practical applications of UV radiation derive from its interactions with organic molecules.

Sunscreen Topical skin product that helps protect against sunburn

Sunscreen, also known as sunblock or sun cream, is a photoprotective topical product for the skin that mainly absorbs, or to a much lesser extent reflects, some of the sun's ultraviolet (UV) radiation and thus helps protect against sunburn and most importantly prevent skin cancer. Sunscreens come as lotions, sprays, gels, foams, sticks, powders and other topical products. Sunscreens are common supplements to clothing, particularly sunglasses, sunhats and special sun protective clothing, and other forms of photoprotection.

Photodynamic therapy 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).

Sun tanning The 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 which can produce a tanning effect without exposure to ultraviolet radiation, known as sunless tanning.

Indoor tanning 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.

Actinic keratosis Medical condition

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. These growths are more common in fair-skinned people and those who are frequently in the sun. They are believed to form when skin gets damaged by UV radiation from the sun or indoor tanning beds, usually over the course of decades. Given their pre-cancerous nature, if left untreated, they may turn into a type of skin cancer called squamous cell carcinoma. Untreated lesions have up to a 20% risk of progression to squamous cell carcinoma, so treatment by a dermatologist is recommended.

PUVA is an ultraviolet light therapy treatment for skin diseases: eczema, psoriasis, graft-versus-host disease, vitiligo, 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.

Psoralen 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.

Photolyase

Photolyases are DNA repair enzymes that repair damage caused by exposure to ultraviolet light. These enzymes require visible light both for their own activation and for the actual DNA repair. The DNA repair mechanism involving photolyases is called photoreactivation. They mainly convert pyrimidine dimers into a normal pair of pyrimidine bases.

Pyrimidine dimer

Pyrimidine dimers are molecular lesions formed from thymine or cytosine bases in DNA via photochemical reactions. Ultraviolet light (UV) induces the formation of covalent linkages between consecutive bases along the nucleotide chain in the vicinity of their carbon–carbon double bonds. The dimerization reaction can also occur among pyrimidine bases in dsRNA —uracil or cytosine. Two common UV products are cyclobutane pyrimidine dimers (CPDs) and 6–4 photoproducts. These premutagenic lesions alter the structure and possibly the base-pairing. Up to 50–100 such reactions per second might occur in a skin cell during exposure to sunlight, but are usually corrected within seconds by photolyase reactivation or nucleotide excision repair. Uncorrected lesions can inhibit polymerases, cause misreading during transcription or replication, or lead to arrest of replication. Pyrimidine dimers are the primary cause of melanomas in humans.

Crosslinking of DNA Crosslinking occurring when various exogenous or endogenous agents react with two nucleotides of DNA

In genetics, crosslinking of DNA occurs when various exogenous or endogenous agents react with two nucleotides of DNA, forming a covalent linkage between them. This crosslink can occur within the same strand (intrastrand) or between opposite strands of double-stranded DNA (interstrand). These adducts interfere with cellular metabolism, such as DNA replication and transcription, triggering cell death. These crosslinks can, however, be repaired through excision or recombination pathways.

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

Solar urticaria Medical condition

Solar urticaria (SU) is a rare condition in which exposure to ultraviolet or UV radiation, or sometimes even visible light, induces a case of urticaria or hives that can appear in both covered and uncovered areas of the skin. It is classified as a type of physical urticaria. The classification of disease types is somewhat controversial. One classification system distinguished various types of SU based on the wavelength of the radiation that causes the breakout; another classification system is based on the type of allergen that initiates a breakout.

Trioxsalen Chemical compound

Trioxsalen 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 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.

Direct DNA damage can occur when DNA directly absorbs a UVB photon, or for numerous other reasons. UVB light causes thymine base pairs next to each other in genetic sequences to bond together into pyrimidine dimers, a disruption in the strand, which reproductive enzymes cannot copy. It causes sunburn and it triggers the production of melanin.

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

Bergapten 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.

Sunburn 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 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, and 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.

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.

Angelicin 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 coumarine.

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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