{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T06:43:44Z","timestamp":1793169824236,"version":"4.5.0"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"20","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,5,16]]},"abstract":"<jats:p>\n                    The\n                    <jats:italic>FHIT<\/jats:italic>\n                    gene has many hallmarks of a tumor-suppressor gene and is involved in a large variety of cancers. We treated A\/J mice and (C57BL\/6J \u00d7 129\/SvJ)F\n                    <jats:sub>1<\/jats:sub>\n                    (B6\/129 F\n                    <jats:sub>1<\/jats:sub>\n                    ) mice, either wild-type or\n                    <jats:italic>FHIT<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    , with multiple doses of benzo[\n                    <jats:italic>a<\/jats:italic>\n                    ]pyrene (B[\n                    <jats:italic>a<\/jats:italic>\n                    ]P) by gavage. B[\n                    <jats:italic>a<\/jats:italic>\n                    ]P caused a time-related increase of micronuclei in peripheral blood erythrocytes. Both A\/J and B6\/129 F\n                    <jats:sub>1<\/jats:sub>\n                    mice, irrespective of their\n                    <jats:italic>FHIT<\/jats:italic>\n                    status, were sensitive to induction of forestomach tumors, whereas B[\n                    <jats:italic>a<\/jats:italic>\n                    ]P induced glandular stomach hyperplasia and a high multiplicity of lung tumors in A\/J mice only. Preneoplastic lesions of the uterus were more frequent in\n                    <jats:italic>FHIT<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice. B6\/129 F\n                    <jats:sub>1<\/jats:sub>\n                    mice underwent spontaneous alopecia areata and hair bulb cell apoptosis, which were greatly accelerated either by\n                    <jats:italic>FHIT<\/jats:italic>\n                    heterozygosity or by B[\n                    <jats:italic>a<\/jats:italic>\n                    ]P treatment, thus suggesting that\n                    <jats:italic>FHIT<\/jats:italic>\n                    plays a role in the pathogenesis of alopecia areata. The oral administration of either budesonide or\n                    <jats:italic>N<\/jats:italic>\n                    -acetyl-\n                    <jats:sc>l<\/jats:sc>\n                    -cysteine (NAC) inhibited the occurrence of this inflammatory skin disease. In addition, these agents prevented B[\n                    <jats:italic>a<\/jats:italic>\n                    ]P-induced glandular stomach hyperplasia and decreased the size of both forestomach tumors and lung tumors in A\/J mice. Budesonide also attenuated lung tumor multiplicity. In B6\/129 F\n                    <jats:sub>1<\/jats:sub>\n                    mice, NAC significantly decreased the proliferating cell nuclear antigen in lung tumors. Both budesonide and NAC inhibited B[\n                    <jats:italic>a<\/jats:italic>\n                    ]P-induced forestomach tumors and preneoplastic lesions of the respiratory tract in B6\/129 F\n                    <jats:sub>1<\/jats:sub>\n                    mice. In conclusion, heterozygosity for\n                    <jats:italic>FHIT<\/jats:italic>\n                    affects susceptibility of mice to spontaneous alopecia areata and B[\n                    <jats:italic>a<\/jats:italic>\n                    ]P-induced preneoplastic lesions of the uterus and does not alter responsiveness to budesonide and NAC.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0601412103","type":"journal-article","created":{"date-parts":[[2006,5,3]],"date-time":"2006-05-03T20:51:10Z","timestamp":1146689470000},"page":"7823-7828","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":21,"title":["Influence of\n                    <i>FHIT<\/i>\n                    on benzo[\n                    <i>a<\/i>\n                    ]pyrene-induced tumors and alopecia in mice: Chemoprevention by budesonide and\n                    <i>N<\/i>\n                    -acetylcysteine"],"prefix":"10.1073","volume":"103","author":[{"given":"Roumen","family":"Balansky","sequence":"first","affiliation":[{"name":"*Department of Health Sciences, University of Genoa, Via A. Pastore 1, I-16132 Genoa, Italy;"},{"name":"National Center of Oncology, Sofia 1756, Bulgaria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"D'Agostini","sequence":"additional","affiliation":[{"name":"*Department of Health Sciences, University of Genoa, Via A. Pastore 1, I-16132 Genoa, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gancho","family":"Ganchev","sequence":"additional","affiliation":[{"name":"National Center of Oncology, Sofia 1756, Bulgaria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Izzotti","sequence":"additional","affiliation":[{"name":"*Department of Health Sciences, University of Genoa, Via A. Pastore 1, I-16132 Genoa, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Di Marco","sequence":"additional","affiliation":[{"name":"*Department of Health Sciences, University of Genoa, Via A. Pastore 1, I-16132 Genoa, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald A.","family":"Lubet","sequence":"additional","affiliation":[{"name":"National Cancer Institute, Rockville, MD 20898; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Zanesi","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo M.","family":"Croce","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvio","family":"De Flora","sequence":"additional","affiliation":[{"name":"*Department of Health Sciences, University of Genoa, Via A. 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