Related Experiment Video
Updated: Aug 6, 2026
Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model
Published on: September 7, 2013
Responses to ultraviolet-B in cell lines from hereditary melanoma kindreds
J A Shannon1, R F Kefford, G J Mann
1Westmead Institute of Cancer Research, University of Sydney at Westmead Millennium Institute, NSW, Australia.
Abstract:
Ultraviolet-B (UV-B) triggers a cascade of events involving cell cycle control genes leading ultimately to DNA repair or apoptosis. The hypothesis examined here is that the genetic abnormality predisposing to melanoma affects the ability of the cell to respond appropriately to UV-B, so favouring mutagenesis. Epstein-Barr virus-transformed lymphoblastoid cell lines from hereditary melanoma kindreds were irradiated with UV-B, and changes in p53, p21 and Bcl-2 expression and cell cycle phase distribution were analysed. Twenty-two cell lines were tested: 12 carriers of melanoma susceptibility and 10 non-carriers (unaffected first degree relatives). At 24 h after irradiation with 50 J/m2, 15 of the 22 cell lines showed a rise in G2/M. After 400 J/m2, all the cell lines showed a reduction or loss of G2/M and 17 of the 22 showed an S phase delay. More carriers than noncarriers of melanoma susceptibility showed significant S phase delay after 50 J/m2 (seven out of 12 carriers versus two out of 10 non-carriers). Six of the 10 pairs (carrier versus non-carrier) tested showed discordant cell cycle responses; however the nature of the difference was not universal. Bcl-2 reduction was seen 4 h post-irradiation in all the carriers and non-carriers. The p53 and p21 responses, although showing some individual variations, were not related to carrier status. These results show individual variations in response to UV-B irradiation among cell lines from the members of hereditary melanoma kindreds, but no consistent differences between carriers and non-carriers of melanoma susceptibility.
Insights
Genetic predisposition to melanoma may alter cellular responses to ultraviolet-B (UV-B) radiation. This study found individual variations in cell cycle control after UV-B exposure, but no consistent differences between melanoma susceptibility carriers and non-carriers.
Area of Science:
- Genetics
- Molecular Biology
- Dermatology
Background:
- Ultraviolet-B (UV-B) radiation induces DNA damage, triggering cell cycle arrest for repair or apoptosis.
- Melanoma susceptibility may involve impaired cellular responses to UV-B, potentially promoting mutagenesis.
- Understanding these responses is crucial for identifying individuals at higher risk for melanoma.
Purpose of the Study:
- To investigate whether genetic predisposition to melanoma affects cellular responses to UV-B irradiation.
- To analyze changes in cell cycle control genes (p53, p21, Bcl-2) and cell cycle phase distribution after UV-B exposure in individuals with and without melanoma susceptibility.
Main Methods:
- Epstein-Barr virus-transformed lymphoblastoid cell lines from hereditary melanoma kindreds (12 carriers, 10 non-carriers) were irradiated with UV-B (50 J/m2 and 400 J/m2).
- Changes in p53, p21, and Bcl-2 expression and cell cycle phase distribution (G2/M, S phase) were analyzed at specific time points post-irradiation.
Main Results:
- UV-B irradiation induced G2/M phase changes and S phase delay in most cell lines.
- A higher proportion of melanoma susceptibility carriers showed significant S phase delay after low-dose UV-B (50 J/m2) compared to non-carriers.
- While Bcl-2 expression decreased in all cell lines, p53 and p21 responses varied individually and were not linked to carrier status.
Conclusions:
- Cell lines from hereditary melanoma kindreds exhibit individual variations in response to UV-B irradiation.
- No consistent, universal differences in cell cycle response to UV-B were observed between carriers and non-carriers of melanoma susceptibility.
- Further research is needed to elucidate the complex interplay between genetic predisposition, UV-B response, and melanoma development.
Related Concept Videos
01:35Mutations
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
01:38Nucleotide Excision Repair
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
01:19Pigmentation
Melanin occurs in two primary forms: eumelanin that provides black and brown pigment and pheomelanin that provides red color. Dark-skinned individuals produce more melanin than those with pale...
01:30Skin Cancer
Basal Cell Carcinoma (BCC): BCC is the most common type of skin cancer, accounting for about 80% of cases. It typically develops in...