Inhibition of UV-Induced p53 Mutations by Sunscreens: Implications for Skin Cancer Prevention

Ananthaswamy, Honnavara N.; Loughlin, Susan M.; Ullrich, Stephen E.; Kripke, Margaret L.

doi:10.1038/jidsp.1998.13

Cited by 19 publications

(23 citation statements)

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“…Most of the mutations detected in the p53 gene in human tumors were UV signature mutations characterized by C-T and CC-TT transitions at dipyrimidine sites (Hartmann et al, 1996). Such UV-type mutations in p53 largely dominate in nonmelanoma skin cancers, which have been linked to a cumulative lifetime exposure to UV (Brash et al, 1996;Ananthaswamy et al, 1998b). The presence of C-T transitions in the p53 gene in CM519 and CM3205 melanomas, initiated by DMBA, and promoted by UV plus croton oil or TPA, indicates that those mutations were most likely induced by chronic UV exposure.…”

Section: Discussionmentioning

confidence: 99%

Genomic alterations in spontaneous and carcinogen-induced murine melanoma cell lines

et al. 2004

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We have conducted an analysis of genetic alterations in spontaneous murine melanoma cell line B16F 0 and its two metastatic clones, B16F 1 and B16F 10 and the carcinogeninduced murine melanoma cell lines CM519, CM3205, and K1735. We found that unlike human melanomas, the murine melanoma cell lines did not have activating mutations in the Braf oncogene at exon 11 or 15. However, there were distinct patterns of alterations in the ras, Ink4a/Arf, and p53 genes in the two melanoma groups. In the spontaneous B16 melanoma cell lines, expression of p16Ink4a and p19 Arf tumor suppressor proteins was lost as a consequence of a large deletion spanning Ink4a/Arf exons 1a, 1b, and 2. In contrast, the carcinogen-induced melanoma cell lines expressed p16 Ink4a but had inactivating mutations in either p19Arf (K1735) or p53 (CM519 and CM3205). Inactivation of p19Arf or p53 in carcinogen-induced melanomas was accompanied by constitutive activation of mitogen-activated protein kinases (MAPKs) and/or mutation-associated activation of N-ras. These results indicate that genetic alterations in p16 Ink4a /p19Arf , p53 and ras-MAPK pathways can cooperate in the development of murine melanoma.

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Section: Discussionmentioning

confidence: 99%

Genomic alterations in spontaneous and carcinogen-induced murine melanoma cell lines

et al. 2004

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“…Another concept for measuring the nonerythema effects of UV radiation is the mutation protection factor. The mutation protection factor is defi ned as the ability of a sunscreen to inhibit p53 mutations for example as induced by UVB irradiation [25] . The number of p53 mutations can be measured by allele-specifi c polymerase chain reaction and immunohistochemical staining detecting mutated p53 protein.…”

Section: Inorganic Sunscreensmentioning

confidence: 99%

Sunscreens – Which and What for?

Maier

Körting²

2005

Skin Pharmacol Physiol

123

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micronization and encapsulation allow the development of high-quality inorganic sunscreens. The potential systemic toxicity of organic sunscreens has lately primarily been discussed controversially in public, and several studies show contradictory results. Although a matter of debate, at present the sun protection factor (SPF) is the most reliable information for the consumer as a measure of sunscreen fi lter effi cacy. In this context additional tests have been introduced for the evaluation of not only the protective effect against erythema but also protection against UV-induced immunological and mutational effects. Recently, combinations of UV fi lters with agents active in DNA repair have been introduced in order to improve photoprotection. This article reviews the efficacy of sunscreens in the prevention of epithelial and nonepithelial skin cancer, the effect on immunosuppression and the value of the SPF as well as new developments on the sunscreen market.

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“…As this p53 mutation is found early during photocarcinogenesis, UVB-induced mutations in p53 can serve as a very early warning of non-melanoma skin cancer induction (40). MPF can be defined by a sunscreen's ability to inhibit p53 mutations and can be measured by molecular biologic methods such as allele-specific polymerase chain reaction and single-strand conformation polymorphism that measures number or incidence of mutation hotspots (40), and/or immunohistochemical stains or Western blots that detect mutated p53 protein (58). A standardized way of calculating MPF would be helpful to develop this technique of measuring sunscreen efficacy.…”

Section: Mutation Protection Factor (Mpf)mentioning

confidence: 99%

“…Around week 16, when the p53 mutation frequency reached maximum, skin cancers began to occur (40). Application of sunscreen inhibited p53 mutations and skin cancer in mice (41).…”

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UV‐induced immune suppression and sunscreen

Gil

Kim

2000

Photoderm Photoimm Photomed

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Sun protection factor (SPF) that measures sunscreen protection against erythema and edema may not be enough to measure a sunscreen's activity against many other biologic reactions induced by ultraviolet radiation (UV). It may be better to evaluate sunscreen efficacy using various tools including immune protection factor (IPF), mutation protection factor (MPF) and protection against photocarcinogenesis. In terms of immune protection, sunscreens protected against UV-induced immune suppression significantly. But protection in some cases was partial and often the IPF of sunscreens were less than the SPF. IPF may differ with various immunological endpoints, and it T he sun emits a wide range of ultraviolet (UV) radiation. All of the harmful UVC (200-280 nm) and most of UVB (280-320 nm) is absorbed by the stratospheric ozone layer. Stratospheric ozone does not affect UVA (320-400 nm) transmission. As the stratospheric ozone layer is depleted (1) the amount of harmful shortwave UV reaching the earth's surface will increase. On the other hand, chances of UV exposure by increased outdoor activity and imprudent use of sun tanning machines increased the risks of unwanted UV effects, such as sunburn, photoaging, skin cancer induction and immune suppression (2). Solar UV is the most prominent cause of skin cancer, a cancer that is the most common cancer found in Caucasian populations. During photocarcinogenesis, UV works as both an initiator by directly damaging DNA and as a promotor by suppressing immunologic rejection (3).Sunscreen use has been promoted as one way to prevent these harmful consequences of UV exposure. The ability of a sunscreen to protect against erythema, the so-called SPF, although well characterized may not be an adequate measure of a sunscreen's ability to protect against other biological endpoints, particularly immune suppression (4). Although there are many examples in the scientific literature regarding sunscreen protection against UV-in-101 may be better to use a couple of different assays to measure sunscreen protection more objectively. Sunscreen use protects against most UV-induced nonmelanoma skin cancers and actinic keratoses but its activity against melanoma is not clear. More studies with broad-spectrum stable sunscreens and better models for the investigation of malignant melanoma are required.

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Inhibition of UV-Induced p53 Mutations by Sunscreens: Implications for Skin Cancer Prevention

Cited by 19 publications

References 0 publications

Genomic alterations in spontaneous and carcinogen-induced murine melanoma cell lines

Genomic alterations in spontaneous and carcinogen-induced murine melanoma cell lines

Sunscreens – Which and What for?

UV‐induced immune suppression and sunscreen

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