Resistance of Pigmented Human Cells to Killing by Sunlight and Oxygen Radicals

Musk, P.; Parsons, Peter G.

doi:10.1111/j.1751-1097.1987.tb04800.x

Cited by 28 publications

(13 citation statements)

References 31 publications

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“…In agreement with other studies, our data revealed that UVR (in the range capable of causing sunburn in vivo) generally induces cell death and a drastic increase in the apoptotic activity in the irradiated WM cell lines, [25][26][27][28] suggesting excessive underlying DNA damage beyond the capacity of the repair system. 29 This DNA damage may be either in the form of accumulated pyrimidine dimers (induced by UVB) or oxidatively modified bases (induced by UVA).…”

Section: Discussionsupporting

confidence: 92%

Genomic instability in radial growth phase melanoma cell lines after ultraviolet irradiation

Hussein

2005

J Clin Pathol

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Background/Aims:Although ultraviolet (UV) irradiation, apoptosis, and genomic instability are all potentially involved in the pathogenesis of melanoma, in vitro studies investigating these changes in the radial growth phase of this neoplasm are still lacking; therefore, this study was designed to investigate these changes.Method:An in vitro system consisting of three radial growth phase Wistar melanoma cell lines (WM35, WM3211, and WM1650) was established. Cells were UV irradiated (10 mJ/cm2for UVB and 6 J/cm2for UVA), harvested after UV exposure, and evaluated for viability and apoptosis using Trypan blue and terminal deoxynucleotidyl transferase mediated dUTP digoxigenin nick end labelling assays, respectively. Polymerase chain reaction based microsatellite assays were used to examine the cell lines for the presence of microsatellite instability (MSI) using 21 markers at the 1p, 2p, 3p, 4q, 9p, and 17p regions.Results:Exposure to UV initiated progressive cell death associated with pronounced apoptosis, with UVA having a greater effect than UVB. MSI was found in UVB (WM35 and WM3211) and UVA (WM35) irradiated cell lines at 1p, 9p, and 17p, but not in non-irradiated cells. The prevalence of MSI was higher after UVB irradiation (14%) than UVA irradiation (4.7%), and was most frequently found at D1S233.Conclusions:The ability of erythemogenic UV irradiation to induce both apoptosis and MSI in radial growth phase melanoma cells is suggestive of its role in melanoma pathogenesis. This instability may reflect a hypermutability state, oxidative stress induced DNA damage, replication infidelity, or a combination of these factors.

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Section: Discussionsupporting

confidence: 92%

Genomic instability in radial growth phase melanoma cell lines after ultraviolet irradiation

Hussein

2005

J Clin Pathol

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“…2). Exposure of cultured human melanoma cells to UVB has resulted in greater resistance of a heavily melanized line as compared with an amelanotic line (9). The first report of a direct effect of UVB on melanocytes, rather than melanoma cells, was based on cultured human cells (10).…”

Section: Resultsmentioning

confidence: 99%

Genetic predisposition of transgenic mouse melanocytes to melanoma results in malignant melanoma after exposure to a low ultraviolet B intensity nontumorigenic for normal melanocytes.

Larue

Dougherty

Mintz

1992

Proc. Natl. Acad. Sci. U.S.A.

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Tyr-SV40E transgenic mice are susceptible to melanoma due to simian virus 40 oncogenic sequences specifically expressed in pigment cells. Skin melanomas form relatively late. Therefore, melanocyte cell lines have been established from very young transgenic animals, when they showed no skin lesions, so that the spontaneous and gradual progress of the cells toward tumorigenesis could be characterized under culture conditions in which wild-type cells of the same inbred strain remain untransformed. Melanocytes of an in vitro transgenic line were irradiated with very low intensities ofultraviolet B (UVB) (280-to 320-nm wavelength) light at culture psages when the cells had not achieved anchorage independence. After a single exposure to 0.7 mJ/cm2 of UVB radiation, the cells became anchorage independent and formed foci at confluence; however, cells propagated from the foci were not tumorigenic.After one exposure to 1.75 mJ/cm2, more numerous and larger foci resulted, and tlb. cells grown from them yielded malignant melanomas in graft hosts. Wild-type melanocytes were not transformed at these UVB doses. At least two genetic changes contributing to malignant conversion-in addition to the initiating effect of the transgene are likey to have occurred, one change leading to anchorage independence and another to further progress toward malignancy. Cells at these stages provide an opportunity to Isolate the relevant genes and identify any molecular defects attributable to UVB. Tumorigenesis after a very low UVB dose in cells where an initiating stimulus is already present suggests that some other stimulus, such as a gene or a carcinogen, might lead to melanoma in conjunction with exposure to relatively little UVB.The projected dramatic increase in skin melanomas, to 1 in 90 Caucasians in the United States by the year 2000 (1), is generally believed to be due to increasing exposure to the UV radiation in sunlight, especially to ultraviolet B (UVB). Epidemiological evidence points to a correlation of high melanoma incidence with fair complexion and with latitudes near the equator (reviewed in ref.2). The tendency ofpatients with xeroderma pigmentosum to develop melanomas and other skin cancers upon exposure to sunlight (3) strongly implicates genetic susceptibility. The identification of pedigrees marked by familial melanoma reinforces the probability of a genetic predisposition (4) that may be due to genes other than the ones in xeroderma. Thus UVB radiation, genetic susceptibility, and melanin level in the skin all seem to play some role in occurrence of melanoma. Yet there is not direct evidence for their contributions; nor is it possible to conduct appropriate experiments on human subjects or to obtain cells readily from genetically identical individuals for experiments in culture.We have previously produced transgenic mice in which the Tyr-SV40E transgene leads to skin and eye melanomas initiated by simian virus 40 oncogenic sequences driven by the tyrosinase gene promoter expressed in pigment cells (5). All the m...

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“…Additionally, highly melanotic melanocytes, but not melanocytes with a low melanin content, exhibited an increase in melanin content following UV exposure (60). Another study comparing melanoma cells with different melanin contents also found that melanotic melanoma cells were more resistant to the cytotoxic effect of UVB than amelanotic melanoma cells (61). Further comparison of the responses of melanoma cells with different melanin contents to UVB showed that the most melanotic cells had the least amount of photoproducts and were most resistant to cytotoxicity (62).…”

Section: Constitutive Melanin Content and The Response Of Cultured Humentioning

confidence: 98%

Cutaneous Photobiology. The Melanocyte vs. the Sun: Who Will Win the Final Round?

Kadekaro

Kavanagh

Wakamatsu

et al. 2003

Pigment Cell Research

163

129

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Solar ultraviolet radiation (UV) is a major environmental factor that dramatically alters the homeostasis of the skin as an organ by affecting the survival, proliferation and differentiation of various cutaneous cell types. The effects of UV on the skin include direct damage to DNA, apoptosis, growth arrest, and stimulation of melanogenesis. Long-term effects of UV include photoaging and photocarcinogenesis. Epidermal melanocytes synthesize two main types of melanin: eumelanin and pheomelanin. Melanin, particularly eumelanin, represents the major photoprotective mechanism in the skin. Melanin limits the extent of UV penetration through the epidermal layers, and scavenges reactive oxygen radicals that may lead to oxidative DNA damage. The extent of UV-induced DNA damage and the incidence of skin cancer are inversely correlated with total melanin content of the skin. Given the importance of the melanocyte in guarding against the adverse effects of UV and the fact that the melanocyte has a low self-renewal capacity, it is critical to maintain its survival and genomic integrity in order to prevent malignant transformation to melanoma, the most fatal form of skin cancer. Melanocyte transformation to melanoma involves the activation of certain oncogenes and the inactivation of specific tumor suppressor genes. This review summarizes the current state of knowledge about the role of melanin and the melanocyte in photoprotection, the responses of melanocytes to UV, the signaling pathways that mediate the biological effects of UV on melanocytes, and the most common genetic alterations that lead to melanoma.

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Resistance of Pigmented Human Cells to Killing by Sunlight and Oxygen Radicals

Cited by 28 publications

References 31 publications

Genomic instability in radial growth phase melanoma cell lines after ultraviolet irradiation

Genomic instability in radial growth phase melanoma cell lines after ultraviolet irradiation

Genetic predisposition of transgenic mouse melanocytes to melanoma results in malignant melanoma after exposure to a low ultraviolet B intensity nontumorigenic for normal melanocytes.

Cutaneous Photobiology. The Melanocyte vs. the Sun: Who Will Win the Final Round?

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