{"id":230062,"date":"2017-01-13T15:53:34","date_gmt":"2017-01-13T17:53:34","guid":{"rendered":"http:\/\/revistapesquisa.fapesp.br\/en\/?p=230062"},"modified":"2017-01-13T15:53:34","modified_gmt":"2017-01-13T17:53:34","slug":"attack-in-the-dark-of-night-2","status":"publish","type":"post","link":"https:\/\/revistapesquisa.fapesp.br\/en\/attack-in-the-dark-of-night-2\/","title":{"rendered":"Attack in the Dark of Night"},"content":{"rendered":"

\"\u00f4B\u00ea\"Montage with photo:\u2002eduardo cesar\u2002| Illustration:\u2002s\u00edrio can\u00e7ado<\/span><\/a>Published in march 2015<\/a><\/em><\/p>\n

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<\/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, a sign of yet another limitation of sunscreens applied to protect the skin 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. 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 research findings, 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 that one approach to reducing this type of damage is the use of sorbic acid, a food additive. However, 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 is already in some cosmetics.<\/p>\n

In early 2012, Bechara received an e-mail from Douglas Brash at Yale University requesting his collaboration in finding a solution to 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. Because of doubts he had, and the subject itself was related to the work of Camila Mano, who\u2019s PhD he was supervising at USP\u2019s Chemistry Institute, he asked Mano to participate in the study, and soon after, to travel to Yale. Mano, who co-authored the article published in Science<\/em>, left Brazil in late 2012 and stayed almost six months, returning in February 2013. Her first task was to familiarize herself with the problem they had been 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 melanin itself might be causing the changes in DNA.<\/p>\n

Quality Control
\nUnder 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 whether the copy matches the original, similar to a spell-checker that replaces the incorrect letters as soon as the words have been written. Other enzymes are also on permanent alert to fix DNA wherever it is broken.<\/p>\n

Commenting in the journal The Scientist<\/em>, David Fisher, a biologist and skin cancer specialist at Boston\u2019s Massachusetts General Hospital 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. However, as this study showed, it can also cause an opposite effect, promoting the formation of pyrimidine dimers (thymine and cytosine) for at least three hours after direct exposure to the sun\u2019s ultraviolet radiation. The resulting impairment of the DNA molecule\u2019s repair mechanisms can result in an increase of 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 such as 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 radiation,\u201d says Mano. She also 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 blondes, than with eumelanin, which forms the melanin in dark 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 \u201cphotochemistry in the dark,\u201d and it was 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 Bechara 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

Melanin also absorbs visible light and then transfers some of its energy to oxygen molecules, generating a highly reactive form, the so-called singlet oxygen. The excited oxygen can react with molecules such as DNA and the cell\u2019s organelles (or functional chambers) and damages them, according to a recent study performed by researchers in S\u00e3o Paulo and Paran\u00e1 (see Pesquisa FAPESP <\/em>Issue n\u00ba\u00a0227<\/em><\/a>).<\/p>\n

Project<\/strong>
\nTriplet excited species in biological systems (n\u00ba 09\/02062-8<\/a>); Grant Mechanism<\/strong> Fellowships in Brazil \u2013 Doctoral; Principal Investigator<\/strong> Etelvino Jos\u00e9 Henriques Bechara (USP and Unifesp); Recipient<\/strong> Camila Marinho Mano (IQ-USP); Investment<\/strong> 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<\/strong>. V. 347, No. 6224, p. 842-47. 2015.<\/p>\n","protected":false},"excerpt":{"rendered":"Melanin 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":[211,210,259],"coauthors":[5968],"class_list":["post-230062","post","type-post","status-publish","format-standard","hentry","category-science","tag-biochemistry","tag-cellular-biology","tag-chemistry"],"acf":[],"_links":{"self":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts\/230062","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=230062"}],"version-history":[{"count":0,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts\/230062\/revisions"}],"wp:attachment":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/media?parent=230062"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/categories?post=230062"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/tags?post=230062"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/coauthors?post=230062"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}