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<record>
<TEI>
<teiHeader>
<fileDesc>
<titleStmt>
<title xml:lang="en">Ultraviolet A within Sunlight Induces Mutations in the Epidermal Basal Layer of Engineered Human Skin</title>
<author>
<name sortKey="Huang, Xiao Xuan" sort="Huang, Xiao Xuan" uniqKey="Huang X" first="Xiao Xuan" last="Huang">Xiao Xuan Huang</name>
<affiliation>
<nlm:aff id="N0x1ebeab0N0x3bd8960"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Bernerd, Francoise" sort="Bernerd, Francoise" uniqKey="Bernerd F" first="Françoise" last="Bernerd">Françoise Bernerd</name>
<affiliation>
<nlm:aff id="N0x1ebeab0N0x3bd8960"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Halliday, Gary Mark" sort="Halliday, Gary Mark" uniqKey="Halliday G" first="Gary Mark" last="Halliday">Gary Mark Halliday</name>
<affiliation>
<nlm:aff id="N0x1ebeab0N0x3bd8960"></nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt>
<idno type="wicri:source">PMC</idno>
<idno type="pmid">19264911</idno>
<idno type="pmc">2671383</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671383</idno>
<idno type="RBID">PMC:2671383</idno>
<idno type="doi">10.2353/ajpath.2009.080318</idno>
<date when="2009">2009</date>
<idno type="wicri:Area/Pmc/Corpus">000990</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000990</idno>
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<biblStruct>
<analytic>
<title xml:lang="en" level="a" type="main">Ultraviolet A within Sunlight Induces Mutations in the Epidermal Basal Layer of Engineered Human Skin</title>
<author>
<name sortKey="Huang, Xiao Xuan" sort="Huang, Xiao Xuan" uniqKey="Huang X" first="Xiao Xuan" last="Huang">Xiao Xuan Huang</name>
<affiliation>
<nlm:aff id="N0x1ebeab0N0x3bd8960"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Bernerd, Francoise" sort="Bernerd, Francoise" uniqKey="Bernerd F" first="Françoise" last="Bernerd">Françoise Bernerd</name>
<affiliation>
<nlm:aff id="N0x1ebeab0N0x3bd8960"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Halliday, Gary Mark" sort="Halliday, Gary Mark" uniqKey="Halliday G" first="Gary Mark" last="Halliday">Gary Mark Halliday</name>
<affiliation>
<nlm:aff id="N0x1ebeab0N0x3bd8960"></nlm:aff>
</affiliation>
</author>
</analytic>
<series>
<title level="j">The American Journal of Pathology</title>
<idno type="ISSN">0002-9440</idno>
<idno type="eISSN">1525-2191</idno>
<imprint>
<date when="2009">2009</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p>The ultraviolet B (UVB) waveband within sunlight is an important carcinogen; however, UVA is also likely to be involved. By ascribing mutations to being either UVB or UVA induced, we have previously shown that human skin cancers contain similar numbers of UVB- and UVA-induced mutations, and, importantly, the UVA mutations were at the base of the epidermis of the tumors. To determine whether these mutations occurred in response to UV, we exposed engineered human skin (EHS) to UVA, UVB, or a mixture that resembled sunlight, and then detected mutations by both denaturing high-performance liquid chromatography and DNA sequencing. EHS resembles human skin, modeling differential waveband penetration to the basal, dividing keratinocytes. We administered only four low doses of UV exposure. Both UVA and UVB induced p53 mutations in irradiated EHS, suggesting that sunlight doses that are achievable during normal daily activities are mutagenic. UVA- but not UVB-induced mutations predominated in the basal epidermis that contains dividing keratinocytes and are thought to give rise to skin tumors. These studies indicate that both UVA and UVB at physiological doses are mutagenic to keratinocytes in EHS.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article">
<pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Am J Pathol</journal-id>
<journal-title>The American Journal of Pathology</journal-title>
<issn pub-type="ppub">0002-9440</issn>
<issn pub-type="epub">1525-2191</issn>
<publisher>
<publisher-name>American Society for Investigative Pathology</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">19264911</article-id>
<article-id pub-id-type="pmc">2671383</article-id>
<article-id pub-id-type="doi">10.2353/ajpath.2009.080318</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Regular Articles</subject>
<subj-group>
<subject>Tumorigenesis and Neoplastic Progression</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Ultraviolet A within Sunlight Induces Mutations in the Epidermal Basal Layer of Engineered Human Skin</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Huang</surname>
<given-names>Xiao Xuan</given-names>
</name>
<xref ref-type="aff" rid="N0x1ebeab0N0x3bd8960">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Bernerd</surname>
<given-names>Françoise</given-names>
</name>
<xref ref-type="aff" rid="N0x1ebeab0N0x3bd8960"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Halliday</surname>
<given-names>Gary Mark</given-names>
</name>
<xref ref-type="aff" rid="N0x1ebeab0N0x3bd8960">*</xref>
</contrib>
<aff id="N0x1ebeab0N0x3bd8960">From the Discipline of Dermatology,
<label>*</label>
Bosch Institute, Sydney Cancer Centre, The University of Sydney, New South Wales, Australia; and L'Oreal Life Sciences Research,
<label></label>
Clichy, France</aff>
</contrib-group>
<pub-date pub-type="ppub">
<month>4</month>
<year>2009</year>
</pub-date>
<volume>174</volume>
<issue>4</issue>
<fpage>1534</fpage>
<lpage>1543</lpage>
<history>
<date date-type="accepted">
<day>13</day>
<month>1</month>
<year>2009</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright © American Society for Investigative Pathology</copyright-statement>
<copyright-year>2009</copyright-year>
</permissions>
<self-uri xlink:title="pdf" xlink:href="zjh00409001534.pdf"></self-uri>
<abstract>
<p>The ultraviolet B (UVB) waveband within sunlight is an important carcinogen; however, UVA is also likely to be involved. By ascribing mutations to being either UVB or UVA induced, we have previously shown that human skin cancers contain similar numbers of UVB- and UVA-induced mutations, and, importantly, the UVA mutations were at the base of the epidermis of the tumors. To determine whether these mutations occurred in response to UV, we exposed engineered human skin (EHS) to UVA, UVB, or a mixture that resembled sunlight, and then detected mutations by both denaturing high-performance liquid chromatography and DNA sequencing. EHS resembles human skin, modeling differential waveband penetration to the basal, dividing keratinocytes. We administered only four low doses of UV exposure. Both UVA and UVB induced p53 mutations in irradiated EHS, suggesting that sunlight doses that are achievable during normal daily activities are mutagenic. UVA- but not UVB-induced mutations predominated in the basal epidermis that contains dividing keratinocytes and are thought to give rise to skin tumors. These studies indicate that both UVA and UVB at physiological doses are mutagenic to keratinocytes in EHS.</p>
</abstract>
</article-meta>
</front>
<floats-wrap>
<fig position="float" id="F1-7970">
<label>Figure 1</label>
<caption>
<p>The regions of microdisseted 50 keratinocytes for DNA sequencing (
<bold>A</bold>
). The 50 suprabasal cells (S1 and S2) were directly overlying the 50 basal layer cells (B1 and B2). About 50% of the microdissected basal cells were in contact with the basement membrane, as this region was limited to the bottom two cell layers. Emission spectra obtained from UVA, UVB, and ssUV sources used in this study (
<bold>B</bold>
).</p>
</caption>
<graphic xlink:href="zjh0040979700001"></graphic>
</fig>
<fig position="float" id="F2-7970">
<label>Figure 2</label>
<caption>
<p>UV radiation does not induce detectable morphological changes in EHS (
<bold>A</bold>
). Fibroblasts (
<bold>arrow</bold>
) encased in a type I collagen lattice provides dermal support for the epidermis. EHS collected on day 11, 3 days after the final of four UV exposures, were fixed and H&E-stained. Distinct basal (
<bold>1</bold>
), spinous (
<bold>2</bold>
), granular (
<bold>3</bold>
), and cornified (
<bold>4</bold>
) layers are recognizable in un-irradiated control, 12.5 J/cm
<sup>2</sup>
UVA-, 0.1 J/cm
<sup>2</sup>
UVB-, and 1.4 J/cm
<sup>2</sup>
ssUV- irradiated EHS. Sections from the same groups of EHS were immunostained for p53 protein (
<bold>B</bold>
). Anti-CPD immunostaining in adult human skin collected 24 hours after UV irradiation (
<bold>C</bold>
) and in UV-irradiated EHS used for mutation detection (
<bold>D</bold>
). Anti-Ki-67 immunostaining in UV-irradiated adult human skin (
<bold>E</bold>
) and in UV-irradiated EHS (
<bold>F</bold>
). p53 positive cells are stained brown. CPD and Ki-67 positive cells are stained red. Scale bar = 25 μm.</p>
</caption>
<graphic xlink:href="zjh0040979700002"></graphic>
</fig>
<fig position="float" id="F3-7970">
<label>Figure 3</label>
<caption>
<p>UVA and UVB induce
<italic>p53</italic>
mutations in EHS. Similar numbers of mutations are induced by UVA, UVB, and ssUV. Each group had four EHS samples, and total mutations in each group are shown, as detected by sequencing.</p>
</caption>
<graphic xlink:href="zjh0040979700003"></graphic>
</fig>
<fig position="float" id="F4-7970">
<label>Figure 4</label>
<caption>
<p>UVA-induced mutations are predominantly at the base of the epidermis. Mutations identified in
<xref rid="F3-7970" ref-type="fig">Figure 3</xref>
were divided into whether they were found in suprabasal or basal layers of epidermis.</p>
</caption>
<graphic xlink:href="zjh0040979700004"></graphic>
</fig>
<fig position="float" id="F5-7970">
<label>Figure 5</label>
<caption>
<p>Types of
<italic>p53</italic>
mutations induced by UV. Mutations from each of the two doses were pooled for each spectrum to give eight EHS per spectrum.</p>
</caption>
<graphic xlink:href="zjh0040979700005"></graphic>
</fig>
<fig position="float" id="F6-7970">
<label>Figure 6</label>
<caption>
<p>Distribution of
<italic>p53</italic>
mutations induced by UV. Mutations from each of the two doses were pooled for each spectrum to give eight EHS per spectrum. Mutations were detected by sequencing in microdissected groups of 50 keratinocytes localized at the suprabasal or basal regions of the epidermis.</p>
</caption>
<graphic xlink:href="zjh0040979700006"></graphic>
</fig>
<table-wrap position="float" id="T1-7970">
<label>Table 1</label>
<caption>
<p>Details of Mutations Detected in Exons 5–9 of
<italic>p53</italic>
in EHS Samples</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th colspan="1" rowspan="1" align="center" valign="bottom">S-E-L
<xref rid="TFN1-1-7970" ref-type="other">*</xref>
</th>
<th colspan="1" rowspan="1" align="center" valign="bottom">Base change</th>
<th colspan="1" rowspan="1" align="center" valign="bottom">Codon & change</th>
<th colspan="1" rowspan="1" align="center" valign="bottom">Mt
<xref rid="TFN1-2-7970" ref-type="other">
<sup></sup>
</xref>
</th>
<th colspan="1" rowspan="1" align="center" valign="bottom">CpG
<xref rid="TFN1-3-7970" ref-type="other">
<sup></sup>
</xref>
</th>
<th colspan="1" rowspan="1" align="center" valign="bottom">Py-Py</th>
</tr>
</thead>
<tbody>
<tr>
<td colspan="6" rowspan="1" align="left" valign="top">12.5 J/cm
<sup>2</sup>
UVA</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top"> 5-5-B1</td>
<td colspan="1" rowspan="1" align="left" valign="top">G:C>A:T</td>
<td colspan="1" rowspan="1" align="center" valign="top">162, ATC to ATT</td>
<td colspan="1" rowspan="1" align="center" valign="top">S</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top">+</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top"> 5-5-B1</td>
<td colspan="1" rowspan="1" align="left" valign="top">A:T>C:G</td>
<td colspan="1" rowspan="1" align="center" valign="top">178, CAC to CCC</td>
<td colspan="1" rowspan="1" align="center" valign="top">M</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top"> 6-6-B1</td>
<td colspan="1" rowspan="1" align="left" valign="top">G:C>C:G</td>
<td colspan="1" rowspan="1" align="center" valign="top">202, CGT to CCT</td>
<td colspan="1" rowspan="1" align="center" valign="top">M</td>
<td colspan="1" rowspan="1" align="center" valign="top">+</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top"> 7-5-S1</td>
<td colspan="1" rowspan="1" align="left" valign="top">A:T>C:G</td>
<td colspan="1" rowspan="1" align="center" valign="top">178, CAC to CCC</td>
<td colspan="1" rowspan="1" align="center" valign="top">M</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top"> 7-5-B2</td>
<td colspan="1" rowspan="1" align="left" valign="top">A:T>C:G</td>
<td colspan="1" rowspan="1" align="center" valign="top">178, CAC to CCC</td>
<td colspan="1" rowspan="1" align="center" valign="top">M</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top"> 8-5-S1</td>
<td colspan="1" rowspan="1" align="left" valign="top">A:T>C:G</td>
<td colspan="1" rowspan="1" align="center" valign="top">178, CAC to CCC</td>
<td colspan="1" rowspan="1" align="center" valign="top">M</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top"> 8-5-B2</td>
<td colspan="1" rowspan="1" align="left" valign="top">A:T>C:G</td>
<td colspan="1" rowspan="1" align="center" valign="top">178, CAC to CCC</td>
<td colspan="1" rowspan="1" align="center" valign="top">M</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="6" rowspan="1" align="left" valign="top">6.25 J/cm
<sup>2</sup>
UVA</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top"> 9-5-S1</td>
<td colspan="1" rowspan="1" align="left" valign="top">A:T>C:G</td>
<td colspan="1" rowspan="1" align="center" valign="top">178, CAC to CCC</td>
<td colspan="1" rowspan="1" align="center" valign="top">M</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top"> 9-5-S2</td>
<td colspan="1" rowspan="1" align="left" valign="top">A:T>C:G</td>
<td colspan="1" rowspan="1" align="center" valign="top">178, CAC to CCC</td>
<td colspan="1" rowspan="1" align="center" valign="top">M</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top"> 9-5-B1</td>
<td colspan="1" rowspan="1" align="left" valign="top">A:T>C:G</td>
<td colspan="1" rowspan="1" align="center" valign="top">178, CAC to CCC</td>
<td colspan="1" rowspan="1" align="center" valign="top">M</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top"> 9-6-S2</td>
<td colspan="1" rowspan="1" align="left" valign="top">G:C>C:G</td>
<td colspan="1" rowspan="1" align="center" valign="top">202, CGT to CCT</td>
<td colspan="1" rowspan="1" align="center" valign="top">M</td>
<td colspan="1" rowspan="1" align="center" valign="top">+</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top"> 11-6-B1</td>
<td colspan="1" rowspan="1" align="left" valign="top">G:C>C:G</td>
<td colspan="1" rowspan="1" align="center" valign="top">222, CCG to CCC</td>
<td colspan="1" rowspan="1" align="center" valign="top">S</td>
<td colspan="1" rowspan="1" align="center" valign="top">+</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top"> 12-5-B1</td>
<td colspan="1" rowspan="1" align="left" valign="top">A:T>C:G</td>
<td colspan="1" rowspan="1" align="center" valign="top">178, CAC to CCC</td>
<td colspan="1" rowspan="1" align="center" valign="top">M</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top"> 12-6-S2</td>
<td colspan="1" rowspan="1" align="left" valign="top">G:C>C:G</td>
<td colspan="1" rowspan="1" align="center" valign="top">222, CCG to CCC</td>
<td colspan="1" rowspan="1" align="center" valign="top">S</td>
<td colspan="1" rowspan="1" align="center" valign="top">+</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="6" rowspan="1" align="left" valign="top">0.1 J/cm
<sup>2</sup>
UVB</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top"> 24-5-S2</td>
<td colspan="1" rowspan="1" align="left" valign="top">A:T>C:G</td>
<td colspan="1" rowspan="1" align="center" valign="top">146, TGG to GGG</td>
<td colspan="1" rowspan="1" align="center" valign="top">M</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top"> 24-5-S2</td>
<td colspan="1" rowspan="1" align="left" valign="top">G:C>C:G</td>
<td colspan="1" rowspan="1" align="center" valign="top">156, CGC to CGG</td>
<td colspan="1" rowspan="1" align="center" valign="top">S</td>
<td colspan="1" rowspan="1" align="center" valign="top">+</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top"> 24-5-B1</td>
<td colspan="1" rowspan="1" align="left" valign="top">G:C>A:T</td>
<td colspan="1" rowspan="1" align="center" valign="top">139, AAG to AAA</td>
<td colspan="1" rowspan="1" align="center" valign="top">S</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top">+</td>
</tr>
<tr>
<td colspan="6" rowspan="1" align="left" valign="top">0.05 J/cm
<sup>2</sup>
UVB</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top"> 25-5-S1</td>
<td colspan="1" rowspan="1" align="left" valign="top">G:C>T:A</td>
<td colspan="1" rowspan="1" align="center" valign="top">148, GAT to TAT</td>
<td colspan="1" rowspan="1" align="center" valign="top">M</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top">+</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top"> 25-5-S2</td>
<td colspan="1" rowspan="1" align="left" valign="top">G:C>T:A</td>
<td colspan="1" rowspan="1" align="center" valign="top">148, GAT to TAT</td>
<td colspan="1" rowspan="1" align="center" valign="top">M</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top">+</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top"> 26-5-S2</td>
<td colspan="1" rowspan="1" align="left" valign="top">G:C>C:G</td>
<td colspan="1" rowspan="1" align="center" valign="top">156, CGC to CGG</td>
<td colspan="1" rowspan="1" align="center" valign="top">S</td>
<td colspan="1" rowspan="1" align="center" valign="top">+</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top"> 26-5-S2</td>
<td colspan="1" rowspan="1" align="left" valign="top">G:C>C:G</td>
<td colspan="1" rowspan="1" align="center" valign="top">158, CGC to CGG</td>
<td colspan="1" rowspan="1" align="center" valign="top">S</td>
<td colspan="1" rowspan="1" align="center" valign="top">+</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top"> 26-5-B1</td>
<td colspan="1" rowspan="1" align="left" valign="top">G:C>C:G</td>
<td colspan="1" rowspan="1" align="center" valign="top">156, CGC to CGG</td>
<td colspan="1" rowspan="1" align="center" valign="top">S</td>
<td colspan="1" rowspan="1" align="center" valign="top">+</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="6" rowspan="1" align="left" valign="top">1.4 J/cm
<sup>2</sup>
ssUV</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top"> 13-5-S2</td>
<td colspan="1" rowspan="1" align="left" valign="top">A:T>C:G</td>
<td colspan="1" rowspan="1" align="center" valign="top">178, CAC to CCC</td>
<td colspan="1" rowspan="1" align="center" valign="top">M</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top"> 13-9-B2</td>
<td colspan="1" rowspan="1" align="left" valign="top">G:C>T:A</td>
<td colspan="1" rowspan="1" align="center" valign="top">312, ACC to ACA</td>
<td colspan="1" rowspan="1" align="center" valign="top">S</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top">+</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top"> 15-9-B2</td>
<td colspan="1" rowspan="1" align="left" valign="top">G:C>A:T</td>
<td colspan="1" rowspan="1" align="center" valign="top">312, ACC to ACA</td>
<td colspan="1" rowspan="1" align="center" valign="top">S</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top">+</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top"> 16-5-S2</td>
<td colspan="1" rowspan="1" align="left" valign="top">A:T>G:C</td>
<td colspan="1" rowspan="1" align="center" valign="top">174, AGG to GGG</td>
<td colspan="1" rowspan="1" align="center" valign="top">M</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top">+</td>
</tr>
<tr>
<td colspan="6" rowspan="1" align="left" valign="top">0.75 J/cm
<sup>2</sup>
ssUV</td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top"> 18-5-S1</td>
<td colspan="1" rowspan="1" align="left" valign="top">A:T>C:G</td>
<td colspan="1" rowspan="1" align="center" valign="top">178, CAC to CCC</td>
<td colspan="1" rowspan="1" align="center" valign="top">M</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top"> 20-5-S1</td>
<td colspan="1" rowspan="1" align="left" valign="top">A:T>C:G</td>
<td colspan="1" rowspan="1" align="center" valign="top">178, CAC to CCC</td>
<td colspan="1" rowspan="1" align="center" valign="top">M</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
<tr>
<td colspan="1" rowspan="1" align="left" valign="top"> 20-5-B2</td>
<td colspan="1" rowspan="1" align="left" valign="top">A:T>C:G</td>
<td colspan="1" rowspan="1" align="center" valign="top">178, CAC to CCC</td>
<td colspan="1" rowspan="1" align="center" valign="top">M</td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
<td colspan="1" rowspan="1" align="center" valign="top"></td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="TFN1-1-7970">
<label>*</label>
<p>S-E-L, indicates sample number, exons and layers. There were 4 EHS per group, 5–8 12.5 J/cm
<sup>2</sup>
UVA, 9–12 6.25 J/cm
<sup>2</sup>
UVA, 21–24 0.1 J/cm
<sup>2</sup>
UVB, 25–28 0.05 J/cm
<sup>2</sup>
UVB, 13–16 1.4 J/cm
<sup>2</sup>
ssUV, and 17–20 0.75 J/cm
<sup>2</sup>
ssUV. S1 and S2 are regions 1 and 2 in the suprabasal layers of the epidermis; B1 and B2 are regions 1 and 2 in the basal layers of the epidermis. </p>
</fn>
<fn id="TFN1-2-7970">
<label></label>
<p>Mt, mutant, S, indicates silent Mt, M, indicates missense Mt. </p>
</fn>
<fn id="TFN1-3-7970">
<label></label>
<p>+ indicates mutations at CpG or Py-Py sites, − indicates mutations outside. </p>
</fn>
</table-wrap-foot>
</table-wrap>
</floats-wrap>
</pmc>
</record>

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