Unanticipated role of melanin in causing carcinogenic cyclobutane pyrimidine dimers

Premi, Sanjay; Brash, Douglas E.

doi:10.1080/23723556.2015.1033588

Cited by 17 publications

(19 citation statements)

References 10 publications

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“…It is known now, that melanin itself plays an important role in the malignant transformation of melanocytes in addition to UV radiation, especially its reddish yellow variety with free oxygen radicals [16]. It could be similar in the case of neuromelanin, which under certain conditions intensifies oxidation processes, inhibits reducing reactions, damages dopaminergic neurons, and generates inflammation induced by phagocytic cells of microglia [13].…”

Section: Discussionmentioning

confidence: 99%

“…It transpires that melanin under the influence of accumulated energy from UVA radiation secondarily damages melanocyte DNA under oxidative stress conditions and paradoxically promotes carcinogenesis of these cells after cessation of the sun's action [15]. During the so-called dark phase, after cessation of UVA action on the skin, energetically excited and oxidised melanin passes from melanosomes, in the form of monomers, to the cell nucleus and induces the formation of pyrimidine dimers of cytosine, damaging the double helix of DNA [16]. DNA damage is greater in the presence of oxygen radicals also formed under UVA influence [17].…”

Section: Melanin and Neuromelaninmentioning

confidence: 99%

“…Inhibition of melanin synthesis and the use of free radical scavengers as well as nitric oxide synthase (NOS) and NADPH oxidase (NOX) inhibitors prevents the formation of pyrimidine dimers of the DNA strand [15]. In summary, melanin, in particular reddish yellow pheomelanin, does not effectively protect against the sun, but promotes DNA mutations and carcinogenesis the more the skin is exposed to UVA radiation in combination with free oxygen radicals [16]. The results of these experimental studies explain the epidemiological data that fair phototypes have an increased risk of melanoma after sunburn in their clinical history [18].…”

Section: Melanin and Neuromelaninmentioning

confidence: 99%

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Odd correlation: Parkinson’s disease and melanoma. What is the possible link?

2019

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Parkinson's disease (PD) is a neurodegenerative disorder, characterised by depletion of dopamine in the striatum and loss of melanin-positive, dopaminergic neurons in the substantia nigra. Melanoma is a skin neoplasm arising from epidermal melanocytes. The epidemiology of melanoma focuses on well-known risk factors such as light skin and hair colour, gender, eye pigmentation, and ultraviolet (UV) exposure. Many studies have suggested an association between Parkinson's disease and melanoma. The mechanism underlying the possible connection between PD and melanoma is not clear and has aroused lots of interest. More interesting is that the link between these two diseases runs both ways. What is the underlying cause of this reciprocal association?Is it due to Parkinson's treatment? Is levodopa the reason for increased incidence of melanoma in people with the neurodegenerative condition? Are there any genetic, immune system irregularities or environmental risk factors that serve as the common denominator between these two conditions? Should we consider melanoma comorbidity with Parkinson's disease and vice versa? Some hypotheses include pigmentation changes in melanin and/or melanin synthesis enzyme like tyrosinase hydroxylase, autophagy deficits, disturbed form of metabolically controlled cell death, and changes of PD-related genes such as Parkin or a-synuclein. Learning more about the relationship between PD and melanoma may lead to a better understanding of each disease and contribute to more effective treatments of both.

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Section: Discussionmentioning

confidence: 99%

Section: Melanin and Neuromelaninmentioning

confidence: 99%

Section: Melanin and Neuromelaninmentioning

confidence: 99%

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Odd correlation: Parkinson’s disease and melanoma. What is the possible link?

2019

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“…Our data linked Signature 38 to the oxidative stress promoting gene Tyrosinase ( TYR, P=1x10 -4 , Jimbow et al 2001) . As Signature 38 is characterised by an excess of C>A mutations, a typical product of reactive oxygen species (ROS) mediated by activity of 8-hydroxy-2′-deoxyguanosine (DFG, 2010), it might represent DNA damage indirectly caused by UV after direct sun exposure due to oxidative damage (Premi and Brash 2016) , with TYR as a possible damage mediator.…”

Section: Associations Between Global Somatic Mutational Signatures Anmentioning

confidence: 99%

Assessing the Gene Regulatory Landscape in 1,188 Human Tumors

Calabrese

Lehmann

Urban

et al. 2017

Preprint

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Cancer is characterised by somatic genetic variation, but the effect of the majority of non-coding somatic variants and the interface with the germline genome are still unknown. We analysed the whole genome and RNA-Seq data from 1,188 human cancer patients as provided by the Pan-cancer Analysis of Whole Genomes (PCAWG) project to map cis expression quantitative trait loci of somatic and germline variation and to uncover the causes of allele-specific expression patterns in human cancers. The availability of the first large-scale dataset with both whole genome and gene expression data enabled us to uncover the effects of the non-coding variation on cancer. In addition to confirming known regulatory effects, we identified novel associations between somatic variation and expression dysregulation, in particular in distal regulatory elements. Finally, we uncovered links between somatic mutational signatures and gene expression changes, including TERT and LMO2 , and we explained the inherited risk factors in APOBEC-related mutational processes. This work represents the first large-scale assessment of the effects of both germline and somatic genetic variation on gene expression in cancer and creates a valuable resource cataloguing these effects.

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“…누적된 DNA손상은 DNA 전사와 번역시 nuceotide excision repair (NER)과정에서 수정되지 않고 전사 또는 번역되어 변형된 단백질을 형성하게 된다. 또 손상된 DNA를 보호하기 위해 melanocyte로부터 tyrosinase의 활성이 증가되어 멜라닌합성이 증가되어 흑화가 진행 된다 [4]. 더 나아가 심각한 UVB 노출은 홍반, 수포 등 의 일광화상과 색소 침착을 유발하며 세포막손상, 피 부암을 유발한다 [5].…”

Section: 서 론unclassified

Effect of Halophilic Bacterium, Haloarcula vallismortis, Extract on UV-induced Skin Change

Kim¹,

Shin²,

Hwang³

et al. 2015

Journal of the Society of Cosmetic Scientists of Korea

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Skin carrys out protective role against harmful outer environment assaults including ultraviolet radiation, heavy metals and oxides. Especially, ultraviolet-B (UVB) light causes inflammatory reactions in skin such as sun burn and erythma and stimulates melanin pigmentation. Furthermore, the influx of UVB into skin cells causes DNA damage in keratinocytes and dermal fibroblasts, inhibition of extracellular matrix (ECM) synthesis which leads to a decrease in elasticity of skin and wrinkle formation. It also damages dermal connective tissue and disrupts the skin barrier function. Prolonged exposure of human skin to UVB light is well known to trigger severe skin lesions such as cell death and carcinogenesis. Haloarcula vallismortis is a halophilic microorganism isolated from the Dead Sea, Its growth characteristics have not been studied in detail yet. It generally grows at salinity more than 10%, but the actual growth salinity usually ranges between 20 to 25%. Because H. vallismortis is found mainly in saltern or salt lakes, there could exist defense mechanisms against strong sunlight. One of them is generation of additional ATP using halorhodopsin which

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Unanticipated role of melanin in causing carcinogenic cyclobutane pyrimidine dimers

Cited by 17 publications

References 10 publications

Odd correlation: Parkinson’s disease and melanoma. What is the possible link?

Odd correlation: Parkinson’s disease and melanoma. What is the possible link?

Assessing the Gene Regulatory Landscape in 1,188 Human Tumors

Effect of Halophilic Bacterium, Haloarcula vallismortis, Extract on UV-induced Skin Change

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