{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:38:42Z","timestamp":1792060722260,"version":"4.4.0"},"reference-count":28,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5429","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[1999,8,6]]},"abstract":"<jats:p>DNA-damaged cells can either repair the DNA or be eliminated through a homeostatic control mechanism termed \u201ccellular proofreading.\u201d Elimination of DNA-damaged cells after ultraviolet radiation (UVR) through sunburn cell (apoptotic keratinocyte) formation is thought to be pivotal for the removal of precancerous skin cells. Sunburn cell formation was found to be dependent on Fas ligand (FasL), a pro-apoptotic protein induced by DNA damage. Chronic exposure to UVR caused 14 of 20 (70 percent) FasL-deficient mice and 1 of 20 (5 percent) wild-type mice to accumulate p53 mutations in the epidermis. Thus, FasL-mediated apoptosis is important for skin homeostasis, suggesting that the dysregulation of Fas-FasL interactions may be central to the development of skin cancer.<\/jats:p>","DOI":"10.1126\/science.285.5429.898","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:42:20Z","timestamp":1027762940000},"page":"898-900","source":"Crossref","is-referenced-by-count":201,"title":["Fas Ligand: A Sensor for DNA Damage Critical in Skin Cancer Etiology"],"prefix":"10.1126","volume":"285","author":[{"given":"Laurie L.","family":"Hill","sequence":"first","affiliation":[{"name":"Department of Immunology, University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allal","family":"Ouhtit","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M.","family":"Loughlin","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret L.","family":"Kripke","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honnavara N.","family":"Ananthaswamy","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie B.","family":"Owen-Schaub","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.280.10.910"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/372773a0"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0596-525"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.1998.00090.x"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81874-7"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.3.2098"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80054-4"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1165"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.182.5.1223"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119174"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.11.2033"},{"key":"e_1_3_1_13_2","unstructured":"Specific pathogen-free C3H\/HeJ mice were purchased from the National Cancer Institute\u2013Frederick Cancer Research Facility Animal Production Area (Frederick MD). C3H\/HeJ gld\/gld male mice were generated from a breeder colony maintained in our facility and housed in a pathogen-free barrier facility accredited by the Association for Assessment and Accreditation of Laboratory Animal Care in accordance with current U.S. Department of Agriculture Department of Health and Human Services and NIH regulations and standards. Animal procedures were approved by the Institutional Animal Care and Use Committee of the University of Texas M.D. Anderson Center. Mice were shaved and UV-irradiated as previously described (23). The UVR source was a bank of six Kodacel\u2013(TA422 cellulose triacetate film 127 \u03bcm thick; Eastman Kodak Rochester NY) filtered FS40 sunlamps (National Biological Twinsberg OH) that remove all UV wavelengths below 290 nm. The irradiance of the Kodacel-filtered sunlamps measured with an IL-700 radiometer with an SE 240 UV-B detector equipped with an A127 quartz diffuser (International Light Newburyport MA) averaged 5.22 W\/m 2 . The UV source was monitored weekly by placing the UV-B detector in a cage equipped with a wire top. Under these conditions mice were exposed to UV-B radiation (2.5 W\/m 2 ). For all experiments mice were exposed to single or multiple doses of UV-B (5 kJ\/m 2 ) corresponding to 2.3 minimal erythemal doses for C3H mice."},{"key":"e_1_3_1_14_2","unstructured":"Formaldehyde-fixed skin biopsies were paraffin-embedded and immunohistochemistry was performed as previously described (27) with polyclonal goat antibody to Fas (X-20) FasL (M-20) (Santa Cruz Biotechnology Santa Cruz CA) or normal goat serum (isotype control) at final dilutions of 1:500. Staining was visualized with stable diaminobenzidine (Research Genetics Huntsville AL). Specificity of staining was confirmed with blocking peptides; preincubation of antibody with specific peptide eliminated all staining. FasL staining was also verified with a monoclonal antibody to FasL (KAY-10; Pharmingen)."},{"key":"e_1_3_1_15_2","unstructured":"Shaved dorsal skins were fixed in buffered 10% formalin and embedded in paraffin. Five-micrometer sections were stained with hematoxylin-eosin and examined by light microscopy. Criteria for scoring sunburn cells were intensely staining eosinophilic cytoplasm pycnotic nuclei and separation from adjacent cells as previously described (2). For each of two to five mice per point 10 hematoxylin-eosin sections from two separate epidermal sections were counted for sunburn cells. Sunburn cell incidence was calculated per linear centimeter of epidermis with coded slides that did not reveal treatment group. No detectable differences between wild-type and gld\/gld mice in morphology organization or thickness were observed in the epidermis."},{"key":"e_1_3_1_16_2","unstructured":"Dorsal skins were fixed in buffered 10% formalin and embedded in paraffin. TUNEL assay was done with a commercially available kit according to the manufacturer's directions (Promega Madison WI). Slides were examined with an Olympus Inverted System Microscope IX70 (Melville NY) and pictures were taken with a Nikon 35-mm camera (magnification \u00d710)."},{"key":"e_1_3_1_17_2","unstructured":"L. L. Hill et al. data not shown."},{"key":"e_1_3_1_18_2","unstructured":"Data can be accessed at www.sciencemag.org\/feature\/data\/1040041.shl"},{"key":"e_1_3_1_19_2","unstructured":"L. L. Hill and L. B. Owen-Schaub unpublished observations."},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.24.14025"},{"key":"e_1_3_1_21_2","first-page":"2961","volume":"53","author":"Kanjilal S.","year":"1993","unstructured":"Kanjilal S., Pierceall W. E., Cummings K. K., Kripke M. L., Ananthaswamy H. N., Cancer Res. 53, 2961 (1993).","journal-title":"Cancer Res."},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1562\/0031-8655(1998)067<0227:MIHSHM>2.3.CO;2"},{"key":"e_1_3_1_23_2","unstructured":"Epidermis from \u223c8-cm 2 pieces of dorsal skin from the midline of each mouse was separated from the dermis by floating the skin dermis side down in phosphate-buffered saline containing 0.25% trypsin for 2 hours at 37\u00b0C followed by mechanical separation and freezing of epidermis. Frozen epidermis was digested in lysis buffer [4 M urea 0.5% N -lauroylsarcosine 10 mM EDTA 0.2 M NaCl and 100 mM tris-HCl (pH 8.0)] containing proteinase K (300 \u03bcg\/ml) and ribonuclease (100 \u03bcg\/ml) at 37\u00b0C overnight. Samples were heated at 60\u00b0 for 15 min and the DNA was extracted with the phenol-chloroform method. The primer sequences used were as follows: codon 270 5\u2032-GGACGGGACAGCTTTGAGGTTT-3\u2032 (forward); codon 275 5\u2032-GTGTTTGTGCCTGCCT-3\u2032 (forward); and 3\u2032 prime end of exon 8 5\u2032-GCCTGCGTACCTCTCTTTGC-3\u2032. The PCR product was resolved on a 6% polyacrylamide gel and visualized on autoradiographic film."},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0597-510"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5239.1189"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.8.1285"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6210958"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.9.1717"},{"key":"e_1_3_1_29_2","unstructured":"We thank L. Eichler for expert technical assistance and M. Duvic and D. McConkey for critical review of this manuscript. This work was supported by grants from the Skin Cancer Foundation American Cancer Society (CIM-96070 to L.O.-S.) and NIH (CA45623 to H.N.A. and CA52457 to L.O-S.). L.L.H. is the recipient of the Crockrell University Cancer Fighters Scientific Achievement Award and an NIH postdoctoral fellowship (F32 AI09351)."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.285.5429.898","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,13]],"date-time":"2024-01-13T08:55:39Z","timestamp":1705136139000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.285.5429.898"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,8,6]]},"references-count":28,"journal-issue":{"issue":"5429","published-print":{"date-parts":[[1999,8,6]]}},"alternative-id":["10.1126\/science.285.5429.898"],"URL":"https:\/\/doi.org\/10.1126\/science.285.5429.898","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,8,6]]}}}