{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:21:09Z","timestamp":1772137269434,"version":"3.50.1"},"reference-count":44,"publisher":"Proceedings of the National Academy of Sciences","issue":"42","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,10,17]]},"abstract":"<jats:p>\n                    The tumor suppressor gene\n                    <jats:italic>p53<\/jats:italic>\n                    is frequently mutated in cigarette smoke (CS)-related lung cancer. The\n                    <jats:italic>p53<\/jats:italic>\n                    binding pattern of carcinogenic polycyclic aromatic hydrocarbons (PAHs) found in CS coincides with the\n                    <jats:italic>p53<\/jats:italic>\n                    mutational pattern found in lung cancer, and PAHs have thus been considered to be major culprits for lung cancer. However, compared with other carcinogenic compounds, such as aldehydes, the amount of PAHs in CS is minute. Acrolein (Acr) is abundant in CS, and it can directly adduct DNA. Acr\u2013DNA adducts, similar to PAH\u2013DNA adducts, induce predominantly G-to-T transversions in human cells. These findings raise the question of whether Acr\u2013DNA adducts are responsible for\n                    <jats:italic>p53<\/jats:italic>\n                    mutations in CS-related lung cancer. To determine the role of Acr\u2013DNA adducts in\n                    <jats:italic>p53<\/jats:italic>\n                    mutagenesis in CS-related lung cancer we mapped the distribution of Acr\u2013DNA adducts at the sequence level in the\n                    <jats:italic>p53<\/jats:italic>\n                    gene of lung cells using the UvrABC incision method in combination with ligation-mediated PCR. We found that the Acr\u2013DNA binding pattern is similar to the\n                    <jats:italic>p53<\/jats:italic>\n                    mutational pattern in human lung cancer. Acr preferentially binds at CpG sites, and this enhancement of binding is due to cytosine methylation at these sequences. Furthermore, we found that Acr can greatly reduce the DNA repair capacity for damage induced by benzo[\n                    <jats:italic>a<\/jats:italic>\n                    ]pyrene diol epoxide. Together these results suggest that Acr is a major etiological agent for CS-related lung cancer and that it contributes to lung carcinogenesis through two detrimental effects: DNA damage and inhibition of DNA repair.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0607031103","type":"journal-article","created":{"date-parts":[[2006,10,9]],"date-time":"2006-10-09T21:02:33Z","timestamp":1160427753000},"page":"15404-15409","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":331,"title":["Acrolein is a major cigarette-related lung cancer agent: Preferential binding at\n                    <i>p53<\/i>\n                    mutational hotspots and inhibition of DNA repair"],"prefix":"10.1073","volume":"103","author":[{"given":"Zhaohui","family":"Feng","sequence":"first","affiliation":[{"name":"Departments of Environmental Medicine, Pathology, and Medicine, New York University School of Medicine, Tuxedo, NY 10987"}]},{"given":"Wenwei","family":"Hu","sequence":"additional","affiliation":[{"name":"Departments of Environmental Medicine, Pathology, and Medicine, New York University School of Medicine, Tuxedo, NY 10987"}]},{"given":"Yu","family":"Hu","sequence":"additional","affiliation":[{"name":"Departments of Environmental Medicine, Pathology, and Medicine, New York University School of Medicine, Tuxedo, NY 10987"}]},{"given":"Moon-shong","family":"Tang","sequence":"additional","affiliation":[{"name":"Departments of Environmental Medicine, Pathology, and Medicine, New York University School of Medicine, Tuxedo, NY 10987"}]}],"member":"341","published-online":{"date-parts":[[2006,10,17]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10081"},{"key":"e_1_3_4_2_2","first-page":"4855","volume":"54","author":"Greenblatt MS","year":"1994","unstructured":"MS Greenblatt, WP Bennett, M Hollstein, CC Harris Cancer Res 54, 4855\u20134878 (1994).","journal-title":"Cancer Res"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/350427a0"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(97)01246-8"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5286.430"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201647"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/92.10.803"},{"key":"e_1_3_4_8_2","first-page":"70","volume-title":"Handbook of Experimental Pharmacology","author":"Hoffman D","year":"1990","unstructured":"D Hoffman, SS Hecht Handbook of Experimental Pharmacology, eds CS Cooper, PL Grover (Springer, Heidelberg), pp. 70\u201374 (1990)."},{"key":"e_1_3_4_9_2","volume-title":"Concise International Chemical Assessment Document No 43","author":"Gomes R","year":"2002","unstructured":"R Gomes, ME Meek, M Eggleton Concise International Chemical Assessment Document No 43 (World Health Organization, Geneva, 2002)."},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-7992(88)90104-2"},{"key":"e_1_3_4_11_2","first-page":"1717","volume":"48","author":"Grafstrom RC","year":"1988","unstructured":"RC Grafstrom, JM Dypbukt, JC Willey, K Sundqvist, C Edman, L Atzori, CC Harris Cancer Res 48, 1717\u20131721 (1988).","journal-title":"Cancer Res"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.16.7491"},{"key":"e_1_3_4_13_2","first-page":"581","volume":"58","author":"Nath RG","year":"1998","unstructured":"RG Nath, JE Ocando, JB Guttenplan, F-L Chung Cancer Res 58, 581\u2013584 (1998).","journal-title":"Cancer Res"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0402794101"},{"key":"e_1_3_4_15_2","author":"Feng Z","year":"2006","unstructured":"Z Feng, W Hu, L Marnett, M-s Tang Mutat Res, in press. 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