{"id":178499,"date":"2015-03-28T17:33:18","date_gmt":"2015-03-28T20:33:18","guid":{"rendered":"http:\/\/revistapesquisa.fapesp.br\/?p=178499"},"modified":"2015-04-28T17:41:06","modified_gmt":"2015-04-28T20:41:06","slug":"attack-in-the-dark-of-night","status":"publish","type":"post","link":"https:\/\/revistapesquisa.fapesp.br\/en\/attack-in-the-dark-of-night\/","title":{"rendered":"Attack in the Dark of Night"},"content":{"rendered":"

\"\"Montage with photo:\u2002Eduardo Cesar\u2002 Illustration: \u2002S\u00edrio Can\u00e7ado<\/span>Skin pigment, known as melanin, can fragment and form highly reactive chemical compounds when impacted by sunlight. According to a study involving Brazilian researchers published in the February 20, 2015 edition of Science<\/i><\/em>, these compounds can damage the structure of the DNA molecule, which sits in the cell\u2019s nucleus, leading to skin cancer. The study says the attack on DNA can continue for more than three hours after direct exposure to sunlight, sign of yet another limitation of sunscreens applied to the skin to guard against the damaging effects of sunlight\u2019s ultraviolet radiation.<\/p>\n

\u201cSunscreen is not going to completely prevent DNA damage, which continues even after sun exposure,\u201d according to chemist Etelvino Bechara, a senior professor at the University of S\u00e3o Paulo (USP), one of the authors of the study and the researcher responsible for several related thematic projects funded by FAPESP on the impact of free radicals (see interview<\/a><\/i><\/em>). This study is also connected to the National Institute of Science and Technology (INCT) for Redox Processes in Biomedicine, coordinated by Ohara Augusto of the USP Chemistry Institute, with the support of FAPESP and the federal government.<\/p>\n

Based on the study, Bechara recommends even more caution with artificial tanning and notes the urgent need for lotion formulas that can prevent the formation of compounds harmful to DNA even after sun exposure. The study suggests one approach to reducing this kind of damage, which is the use of sorbic acid, a food additive, although its effectiveness, dose and method of application have not yet been determined. Another possible way to minimize sun damage, aside from using ultraviolet radiation filters, would be to use Vitamin E, which some cosmetics already contain.<\/p>\n

In early 2012, Bechara received an e-mail from Douglas Brash at Yale University requesting his collaboration in finding a solution to some problems related to DNA damage in melanocytes, the cells that produce melanin. The damage was associated with the onset of melanoma, an aggressive form of skin cancer. Since doubts he had and the subject itself were related to Camila Mano\u2019s PhD work, which he was supervising at USP\u2019s Chemistry Institute, he asked Mano to participate in the study, and soon after, to prepare to travel to Yale. Mano, who also co-authored the article published in Science<\/i><\/em>, left Brazil in late 2012 and stayed almost six months, returning in February 2013. Her first task was to familiarize herself better with the problem they were unable to solve.<\/p>\n

\u201cThey saw changes in DNA that appeared to have been caused by the sun\u2019s radiation, but which happened after sun exposure,\u201d says Mano. After clarifying her understanding of the problem, she learned how to work with mouse cells and began experiments that might lead to an answer. The initial testing was unsuccessful, but soon she concluded that the melanin itself might be causing the changes in DNA.<\/p>\n

Quality Control
\n<\/b><\/strong>Under normal conditions, the sun\u2019s ultraviolet radiation forms so-called dimers (chemical compounds consisting of two units) of thymine and cytosine, which are two of DNA\u2019s basic components, in melanin-producing cells. The dimers can change how DNA works when the cell multiplies. Luckily, there is a rigorous quality control process that undoes part of the dimers. During DNA replication, some proteins \u2013 repair enzymes \u2013 verify if the copy matches the original, like a spell check that replaces the incorrect letters as soon as the words have been written. Other enzymes are on permanent alert to fix DNA wherever it is broken.<\/p>\n

Commenting in the journal The Scientist<\/i><\/em>, David Fisher, a biologist specializing in skin cancer at Boston\u2019s Massachusetts General Hospital in the United States who was not involved in the study, called the study \u201cvery interesting and provocative.\u201d Fisher continues: \u201cIt emphasizes yet again what we knew: the biochemistry of melanin is a double-edged sword.\u201d Melanin, the skin\u2019s dark pigment, can prevent the formation of dimers. As this study showed, it can also cause the opposite effect, leading to the formation of pyrimidine dimers (thymine and cytosine) for at least three hours after direct exposure to the sun\u2019s ultraviolet radiation, thereby reducing the effectiveness of the DNA molecule\u2019s repair mechanisms, which promotes an increase in harmful genetic mutations.<\/p>\n

Through experiments conducted at Yale and USP, researchers confirmed that ultraviolet radiation sets off the production of a series of enzymes that will generate reactive oxygen species like superoxide or nitric oxide. They combine to form peroxynitrite, a compound that is known to be reactive and that degrades the molecules with which it interacts inside the cell. The reaction between peroxynitrite and melanin or its precursors generates high-energy compounds, which are transferred to DNA, forming the dimers.<\/p>\n

\u201cUltraviolet radiation only initiates these reactions, which can continue for hours, even after only 10 minutes of cell exposure to the radiation,\u201d says Mano. She says that the formation of reactive compounds is more intense with a precursor of melanin called pheomelanin, which is found in the cells of redheads or blonds, than with eumelanin, which forms the melanin in black skin. This would explain why light-skinned people are more susceptible to skin cancer. In the experiment, researchers also verified that the pyrimidine dimers formed in the absence of light make up almost 50% of the dimers responsible for possible changes in DNA.<\/p>\n

This phenomenon is called photochemistry in the dark, and Bechara emphasizes that it had been proposed in the 1970s by Emil White, at Johns Hopkins University, and Giuseppe Cilento, at the USP Chemistry Institute. \u201cPhotochemistry in the dark intensifies the damaging reactions to DNA that are initiated by ultraviolet radiation,\u201d he says. The researcher believes that this type of reaction has been identified in biological phenomena, mediated by high-energy chemical compounds in plant roots and the internal organs of animals.<\/p>\n

\u200bMelanin also absorbs visible light and then transfers some of its energy to oxygen molecules, generating highly reactive forms, the so-called singlet oxygen. The excited oxygen can react with molecules like DNA and the cell\u2019s organelles (or chambers) and damages them, according to a recent study done by researchers in S\u00e3o Paulo and Paran\u00e1 (see Pesquisa FAPESP <\/i><\/em>Issue No. 227<\/i><\/em><\/a>).<\/p>\n

Project<\/strong>
\nTriplet excited species in biological systems (No 09\/02062-8<\/a>); Grant Mechanism<\/b><\/strong> Scholarships in Brazil — Doctoral; Principal Investigator<\/b><\/strong> Etelvino Jos\u00e9 Henriques Bechara (USP and Unifesp); Grant recipient<\/b><\/strong> Camila Marinho Mano (IQ-USP); Investment R$156.227,65 (FAPESP).<\/p>\n

Scientific Article<\/em>
\nPREMI, S. et al<\/em>. Chemiexcitation of melanin derivatives induces DNA photoproducts long after UV exposure<\/a>. Science<\/b><\/strong>. V. 347, No. 6224, p. 842-47. 2015.<\/p>\n","protected":false},"excerpt":{"rendered":"Fragments formed hours after sun exposure may damage DNA","protected":false},"author":17,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_exactmetrics_skip_tracking":false,"_exactmetrics_sitenote_active":false,"_exactmetrics_sitenote_note":"","_exactmetrics_sitenote_category":0,"footnotes":""},"categories":[159],"tags":[237],"coauthors":[5968],"class_list":["post-178499","post","type-post","status-publish","format-standard","hentry","category-science","tag-genetics"],"acf":[],"_links":{"self":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts\/178499","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/users\/17"}],"replies":[{"embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/comments?post=178499"}],"version-history":[{"count":0,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts\/178499\/revisions"}],"wp:attachment":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/media?parent=178499"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/categories?post=178499"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/tags?post=178499"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/coauthors?post=178499"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}