Pigment-producing cells in the skin protect against sunlight and genetic damage


Single periods of sun exposure or radiation therapy to the skin likely pose a minimal risk of skin cancer. This is suggested in a study from IGP where the researchers have shown that pigment-producing cells in the skin can skin can tolerate long-term exposure of genetic injuries by changing between different degrees of maturity.

Melanocytes are pigment-producing cells regularly scattered in the bottom cell layer of the epidermis, adjacent to the dermis. When the skin is exposed to sunlight the cells are exposed to UV radiation that can damage their DNA. To protect the cells both in the epidermis and dermis, the melanocytes produce pigment that also spreads to adjacent skin cells, resulting in a protective tan.

The UV radiation results in the production of free radicals which can damage the DNA and the pigment protects the cells by absorbing the free radicals. Despite this, damage occurs to DNA, but will mostly be repaired satisfactorily. However, in case of repeated solar radiation for many years, the risk of accumulation of unrepaired DNA damage increases. This can result in mutations that transform normal skin cells into tumour cells which divide without control, leading to skin cancer. The most dangerous form is malignant melanoma which occurs when melanocytes are transformed to tumour cells.

In the current study, the researchers have studied how the melanocytes respond to ionising radiation, i.e. the kind of radiation used in cancer radiotherapy, which causes similar DNA damages as UV radiation.

“We have studied tissue samples from cancer patients who underwent radiotherapy. The samples were taken before, during and after the treatment with during daily radiation doses for five weeks. We found that skin melanocytes cope with and survive long-term exposure of genetic injuries,” says Per Fessé, former doctoral student at IGP and first author of the article.

Skin melanocytes have different degrees of maturity. In the study, the researchers could show that upon radiation exposure the immature melanocytes revealed maturity and pigment synthesis, which also increased in the more mature melanocytes.

“What happens after the exposure of DNA damage is ended has not yet been described. We could demonstrate that the melanocytes return to a more immature state. Five weeks after treatment approximately thirty per cent of the melanocytes were immature, which is the same level as before the radiation, and the tan was almost gone. We interpret this as that a single longer period of sun exposure or radiation therapy to the skin poses no or minimal risk of skin cancer,” says Per Fessé.

The researchers also showed that melanocytes live for a long time which allows repeated sun exposures to the same cells over time. The findings strongly suggest that malignant melanoma is most likely caused by unrepaired DNA injuries accumulated from repeated sun exposures over a long period of time in the immature melanocytes.

“We also know that that intermittent sun light exposure increases the risk of malignant melanom, compared to continuous exposure. The latter supports a more higher maturation degree of the melanocytes, which decreases the vulnerability to genetic damage,” says Per Fessé.

It is already known that the cells in the epidermis that surround the melanocytes need to be protected from sun exposure and that they regulate the pigment production in the melanocytes by molecular signaling. In the study, the researchers could identify two important proteins that are used by the surrounding cells to control the degree of maturity of the melanocytes, and that makes them very tolerant to DNA damage from both UV and ionising radiation while the radiation is on-going.

“This fact underlines the interdependence of the melanocytes and their surrounding cells in epidermis to provide a protective mechanism against sunshine and genetic damage. This is knowledge that could not be obtained through laboratory studies of melanocytes in cell cultures,” says Ingela Turesson who led the study.

The study was performed in collaboration with Jan Nyman and Ingegerd Hermansson, University of Gothenburg, Maj-Lis Book, IGP, and Johan Ahlgren, Örebro University. It was recently published in the journal iSience.

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Article in iScience

Last modified: 2022-01-26