Sunlight and skin cancer: Inhibition of p53 mutations in UV-irradiated mouse skin by sunscreens

Ananthaswamy, Honnavara N.; Loughlin, Susan M.; Cox, Pat; Evans, Robert B.; Ullrich, Stephen E.; Kripke, Margaret L.

doi:10.1038/nm0597-510

Cited by 207 publications

(165 citation statements)

References 32 publications

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“…To date, the biological activity of sunscreens in offering protection against erythema has been represented through the use of a Sun Protection Factor (SPF). Some investigators have recently shown that SPF is not an adequate gauge when evaluating a sunscreen's ability to protect against UV-induced biological activity, and they propose estimating the protective activity of sunscreen through the use of other categories [10,11,[22][23][24]. In this study we examined Drosophila systems to determine if a genotoxicity protection factor could be utilized as an alternative evaluation of the efficacy of a sunscreen.…”

Section: Discussionmentioning

confidence: 99%

“…Gill and Kim proposed the Immune Protection Factor (IPF) as a measure of the effectiveness of a sunscreen to protect against UV-induced immune suppression [9]. Ananthaswamy et al proposed the Mutation Protection Factor (MPF) as an estimate of a sunscreen's protective activity, as obtained through the measurement of p53 mutation in the skin of mice irradiated with UVB [10]. It has also been shown that treatment with sunscreen reduced the incidence of tumors in the skin of mice irradiated by a solar simulator [11].…”

Section: Introductionmentioning

confidence: 99%

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Alternative methods to evaluate the protective ability of sunscreen against photo-genotoxicity

Toyoshima

Hosoda

Hanamura

et al. 2004

Journal of Photochemistry and Photobiology B: Biology

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Numerous epidemiological investigations show that sunlight is carcinogenic to humans and that the use of sunscreen may be effective in decreasing the risk of skin cancer. The biological activity of a sunscreen is evaluated by its ability to protect human skin from erythema as represented by an SPF (Sun Protection Factor). We propose that the sunscreen's protective effect against sunlight-induced genotoxicity, including mutation, should also be taken into account. In this study we examined the protective ability of sunscreens against natural sunlight and UV-induced genotoxicity in Drosophila somatic cells. We prepared three kinds of sunscreen samples, each with an SPF value of 20, 40 or 60, and compared their protective activities with commercial sunscreens. When a sunscreen of SPF 20, 40 or 60 was pasted on the plastic cover of a petri dish in which Drosophila larvae were exposed to the sun or UV lamps, genotoxicity decreased as the SPF of the sunscreen increased, relative to levels of genotoxicity observed in samples without sunscreen. However, the protective abilities of sunscreens were unexpectedly not so different from each other. To reveal the relationship between the protective activity of sunscreen and the wavelength of light with which larvae were irradiated through the sunscreen, we measured the transmittance of light through the petri dish cover on which the sunscreen was pasted. Effective protection was demonstrated by removing components of light whose wavelengths were below 315 nm. We suggest that the measurement of antigenotoxic activity and the determination of the wavelengths of light transmitted through the sunscreen should be an alternative method for evaluating the effectiveness of a sunscreen.2

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Alternative methods to evaluate the protective ability of sunscreen against photo-genotoxicity

Toyoshima

Hosoda

Hanamura

et al. 2004

Journal of Photochemistry and Photobiology B: Biology

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“…Oral consumption of ␣-difluoromethylornithine, an irreversible specific inhibitor of ODC, in the drinking water (1% w/v) to the transgenic mice resulted in complete prevention of UVB-mediated tumorigenesis and a substantial decrease in the formation of pigmented cysts Excessive exposure of skin to ultraviolet (UV) light, particularly in the middle wavelength range (UVB; 290 to 320 nm), elicits a variety of adverse effects that include skin aging, cutaneous inflammation, erythema, immunosuppression, cell death, and skin cancer. [1][2][3][4][5][6] More than a million new cases of nonmelanoma skin cancers, which include basal cell carcinoma and squamous cell carcinoma (both derived from epidermal keratinocytes), are diagnosed annually in the United States. 6,7 Unlike chemically induced skin carcinogenesis, UV is a complete carcinogen with both tumor-initiating as well as tumorpromoting effects.…”

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confidence: 99%

A Definitive Role of Ornithine Decarboxylase in Photocarcinogenesis

Ahmad

Gilliam

Katiyar

et al. 2001

The American Journal of Pathology

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Excessive exposure of solar ultraviolet (UV) radiation, particularly its UVB component, to human skin is the major cause for more than a million new cases of cutaneous malignancies diagnosed annually in the United States. Photocarcinogenesis, like other cancers, is a multistep process that includes initiation and promotion. A proper understanding of the molecular events occurring during the tumor promotion phase of photocarcinogenesis could lead to the development of novel approaches for the management of skin cancer. Using a transgenic mouse model (K5/ODC mice), which overexpresses the enzyme ornithine decarboxylase (ODC) in hair follicle keratinocytes, we studied the role of this gene in photocarcinogenesis. A single UVB-exposure of 180 mJ/cm 2 to the transgenic mice resulted in a minimal increase in bifold skin thickness and ODC activity. However, in SKH-1 hairless mice, the most common and highly sensitive model for photocarcinogenesis, and in littermate nontransgenic mice, increases in skin thickness and ODC activity were substantial. In long-term experiments, mice were exposed to 180 mJ/cm 2 of UVB radiation three times a week for 2 weeks (tumorinitiating dose). At 30 weeks after this treatment, in two independent experiments, 40% of the K5/ODC transgenic mice exposed to UVB were found to develop epidermal tumors. The tumors were histologically verified as benign papillomas and squamous cell carcinomas. Interestingly, 100% of the transgenic mice also developed >20 pigmented cysts/mouse, which contained keratinocyte material with increased keratinocytic melanization.

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“…The 5'?3' sequence is read from bottom to top Figure 2 p53 mutations at codon 270 arise early in UVirradiated XPC7/7 and XPC+/+ mouse skin. Mice were irradiated ®ve times per week (Monday through Friday) for 1 ± 4 weeks at a dose of 2.5 kJ/m 2 UVB per exposure from a bank of six FS40 sunlamps, as described before (Ananthaswamy et al, 1997). Epidermal DNA (360 ng) was ampli®ed by polymerase chain reaction (PCR) using the mutant-speci®c primers 5'-GGACGGGACAGCTTTGAGGTTT-3' and 5'-GCCTGCG-TACCTCTCTTTGC-3', as described previously (Ananthaswamy et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

“…Mice were irradiated ®ve times per week (Monday through Friday) for 1 ± 4 weeks at a dose of 2.5 kJ/m 2 UVB per exposure from a bank of six FS40 sunlamps, as described before (Ananthaswamy et al, 1997). Epidermal DNA (360 ng) was ampli®ed by polymerase chain reaction (PCR) using the mutant-speci®c primers 5'-GGACGGGACAGCTTTGAGGTTT-3' and 5'-GCCTGCG-TACCTCTCTTTGC-3', as described previously (Ananthaswamy et al, 1997). An aliquot (5 ml) of the PCR product was electrophoresed on a 6% polyacrylamide gel, and the gel was dried and exposed to autoradiographic ®lm.…”

Section: Introductionmentioning

confidence: 99%

Persistence of p53 mutations and resistance of keratinocytes to apoptosis are associated with the increased susceptibility of mice lacking the XPC gene to UV carcinogenesis

et al. 1999

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Like xeroderma pigmentosum (XP) patients, transgenic mice lacking nucleotide excision repair (NER) genes such as XPA and XPC are extremely susceptible to ultraviolet (UV)-induced skin cancer. Because the p53 gene is an important target for UV carcinogenesis and because the p53 protein modulates NER, we investigated the consequences of NER de®ciency on UV-induced p53 mutations in XPC7/7 mouse skin tumors. Thirty-eight (76%) of 50 UV-induced XPC7/7 skin tumor analysed displayed C?T or CC?TT transitions at dipyrimidine sites on the untranscribed strand of the p53 gene. A major hot spot for p53 mutation occurred at codon 270, which is also a hot spot in UV-induced skin tumors from NER-pro®cient C3H and SKH-hr 1 mice. Interestingly, codon 270 mutations were induced in both XPC7/7 and +/+ mouse skin after 1 week of UV irradiation, but the mutations persisted only in XPC7/7 mouse skin after 3 ± 4 weeks of chronic UV. The persistence of UV-induced p53 mutations in XPC7/7 mouse skin was associated with decreased apoptosis and increased proliferation of keratinocytes, suggesting that these events may contribute to the accelerated development of UV-induced skin tumors in XPC7/7 mice.

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Sunlight and skin cancer: Inhibition of p53 mutations in UV-irradiated mouse skin by sunscreens

Cited by 207 publications

References 32 publications

Alternative methods to evaluate the protective ability of sunscreen against photo-genotoxicity

Alternative methods to evaluate the protective ability of sunscreen against photo-genotoxicity

A Definitive Role of Ornithine Decarboxylase in Photocarcinogenesis

Persistence of p53 mutations and resistance of keratinocytes to apoptosis are associated with the increased susceptibility of mice lacking the XPC gene to UV carcinogenesis

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