LONDON ¿ The sunblock creams of the future could contain natural chemicals that enhance cells¿ own abilities to repair the DNA damage wrought by the sun, according to a study done by scientists in Germany and the Netherlands.

The study found that the cytokine interleukin-12 (IL-12) can rescue skin cells that have been exposed to ultraviolet radiation (UV). These cells normally self-destruct because of the damage done to their DNA.

Thomas Schwarz, professor of dermatology at the University of M|nster in Germany, told BioWorld International: ¿I am not saying that IL-12 is the big sunscreen of tomorrow, because it¿s a big molecule, unlikely to be absorbed well through the skin, and it¿s expensive. Nevertheless, it is tempting to speculate about the potential therapeutic or prophylactic applications of our finding, because there might be other ways of achieving the same effect with other molecules which are smaller and can penetrate the skin more easily.¿

Schwarz, together with colleagues at the University of M|nster, at the University of D|sseldorf in Germany, and at the National Institute of Public Health and the Environment at Bilthoven, the Netherlands, reports his results in a paper that will appear in the January edition of Nature Cell Biology. Its title: ¿Interleukin-12 suppresses ultraviolet radiation-induced apoptosis by inducing DNA repair.¿

When cells of the epidermis are exposed to UVB radiation, they respond by undergoing apoptosis. This is the body¿s way of killing off cells whose DNA has been damaged so badly that they threaten to become malignant.

The German/Dutch team embarked on a series of studies investigating the influence of a range of cytokines on this UV-induced apoptosis. Schwarz said, ¿We had already observed, for example, that interleukin-1 enhances UV-induced apoptosis so we were checking out other cytokines, including IL-12.¿

To their surprise, they found that IL-12 protected cells from UV-induced apoptosis. Their first reaction, Schwarz said, was that this was a detrimental effect, because allowing damaged cells to survive could increase the chances of malignant cells¿ persisting. So they set out to identify what mechanism was involved.

¿The result was totally unexpected,¿ Schwarz said. ¿We found that these cells survived because DNA damage ¿ the major trigger for apoptosis ¿ was reduced.¿

When epithelial cells are exposed to UVB radiation, one of the two main types of DNA fragments produced is called cyclobutane pyrimidine dimers (CPDs). These molecules can be detected using an antibody directed against them. This test showed that 3.5 hours after epithelial cells had been irradiated, levels of CPDs were significantly lower if the cells had been treated with IL-12 than if they had not. Yet 10 minutes after irradiation, levels of CPDs were the same in cells that had been treated with IL-12 as in the cells that had not.

Schwarz said, ¿From this result, we could conclude that initially DNA damage is the same, but in the presence of IL-12 the DNA damage is somehow reversed.¿

Other experiments also proved, he said, that IL-12 did not have its effect by filtering out harmful irradiation. In addition, the team was able to reproduce similar results when they examined biopsies of skin from live animals.

A further batch of experiments suggested that the mechanism by which the DNA repair took place was nucleotide excision repair. The team decided to examine what the effect of IL-12 would be in knockout mice ¿ an animal model for the human disease xeroderma pigmentosum. People with this disease are prone to skin malignancies because they are unable to carry out normal nucleotide excision repair. Mice that lack a fully functional copy of the gene Xpa, similarly, cannot perform nucleotide excision repair at normal levels.

Sixteen hours after irradiating a patch of skin on the Xpa knockout mice, the team took biopsies and counted the number of apoptotic cells. Giving wild-type mice IL-12 before the experiment significantly reduced the number of apoptotic cells, but the researchers saw no such reduction in the knockout mice.

Schwarz told BioWorld International: ¿Although I admit that we cannot rule out that another unknown pathway may be involved as well, we feel that the experiment with the Xpa knockout mice is really quite convincing, suggesting that the mechanism by which IL-12 has its protective effect is via nucleotide excision repair.¿

He is now planning studies with IL-12 knockout mice, to find out if they are more likely to develop skin malignancies when exposed to UVB irradiation and, if so, whether application of IL-12 to their skin can prevent this.