{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:47:23Z","timestamp":1792082843062,"version":"4.4.0"},"reference-count":57,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,4,30]],"date-time":"2009-04-30T00:00:00Z","timestamp":1241049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2010,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Sulfur dioxide (SO<jats:sub>2<\/jats:sub>) and benzo(a)pyrene (B(a)P) are common industrial and environmental contaminants. However, few data are available on the effects of SO<jats:sub>2<\/jats:sub>on proto\u2010oncogenes and tumor suppressor genes, as well as the interactions between SO<jats:sub>2<\/jats:sub>and other xenobiotics regulating proto\u2010oncogenes or tumor suppressor genes expression. To investigate the interactions between SO<jats:sub>2<\/jats:sub>and B(a)P, male Wistar rats were exposed to intratracheally instilled with B(a)P or SO<jats:sub>2<\/jats:sub>inhalation alone or together. We detected mRNA expression of<jats:italic>CYP1A1<\/jats:italic>and<jats:italic>1A2<\/jats:italic>, 7\u2010ethoxyresorufin<jats:italic>O<\/jats:italic>\u2010deethylase (EROD), and methoxyresorufin<jats:italic>O<\/jats:italic>\u2010demethylase (MROD) activities in livers. The mRNA and protein levels of several cancer\u2010related genes were analyzed in livers by real\u2010time RT\u2010PCR and Western blot, respectively. The EROD\/MROD activities and<jats:italic>CYP1A1\/2<\/jats:italic>expression were down\u2010regulated by SO<jats:sub>2<\/jats:sub>but up\u2010regulated by B(a)P alone. Exposure of SO<jats:sub>2<\/jats:sub>alone induced c\u2010fos, c\u2010jun, c\u2010myc, H\u2010ras, and p53 expression, and depressed p16 and Rb expression in livers. The effects of B(a)P on the above gene were similar to SO<jats:sub>2<\/jats:sub>except c\u2010fos expression. Furthermore, SO<jats:sub>2<\/jats:sub>+ B(a)P exposure increased the expression of c\u2010fos, c\u2010jun, c\u2010myc, and p53, and decreased p16 and Rb expression in livers compared with exposed to SO<jats:sub>2<\/jats:sub>or B(a)P alone. However, no synergistic effects were observed on H\u2010ras and CYP1A1\/2 after SO<jats:sub>2<\/jats:sub>+ B(a)P exposure. Our findings indicate that multiple cell cycle regulatory proteins play key roles in the toxicity of SO<jats:sub>2<\/jats:sub>and B(a)P in livers. It might involve the activation of c\u2010fos, c\u2010jun, c\u2010myc, and p53. And p16\u2010Rb pathway might also participate in the progress. Although the gene products we studied are classed as oncogenes and tumor suppressor genes, their functions actually relate to more general processes of control of cell proliferation, survival, and\/or apoptosis. \u00a9 2009 Wiley Periodicals, Inc. Environ Toxicol, 2010.<\/jats:p>","DOI":"10.1002\/tox.20484","type":"journal-article","created":{"date-parts":[[2009,4,30]],"date-time":"2009-04-30T11:54:24Z","timestamp":1241092464000},"page":"169-179","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Sulfur dioxide and benzo(a)pyrene modulates CYP1A and tumor\u2010related gene expression in rat liver"],"prefix":"10.1002","volume":"25","author":[{"given":"Guohua","family":"Qin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqiang","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,4,30]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0887-2333(00)00004-7"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2005.08.016"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/53.2.264"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.2307\/3434924"},{"key":"e_1_2_1_6_1","first-page":"259","article-title":"Acetaminophen\u2010induced hepatoxicity is associated with early changes in AP\u20101 DNA binding activity","volume":"92","author":"Blazka ME","year":"1996","journal-title":"Res Commun Mol Pathol Pharmacol"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_1_8_1","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1124\/mol.52.6.974","article-title":"Identification of benzo(a)pyreneinducible cis\u2010acting elements within c\u2010Ha\u2010ras transcriptional regulatory sequences","volume":"52","author":"Bral CM","year":"1997","journal-title":"Mol Pharmacol"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02724044"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(85)90355-7"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.11342"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/20.4.663"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.20023"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0045-6535(95)00305-R"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2184.1994.tb01424.x"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1039\/b106209n"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.2307\/3431613"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx00013a010"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx700252n"},{"key":"e_1_2_1_20_1","first-page":"6304","article-title":"Participation of p53 protein in the cellular response to DNA damage","volume":"51","author":"Kastan MB","year":"1991","journal-title":"Cancer Res"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(99)00154-8"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(97)04610-7"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(20000215)85:4<498::AID-IJC9>3.0.CO;2-F"},{"key":"e_1_2_1_24_1","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1177\/096032719801701103","article-title":"Functional responses of human neutrophils to sodium sulfite (Na2SO3) in vitro","volume":"17","author":"Labbe' P","year":"1998","journal-title":"Hum Exp Toxicol"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2005.12.020"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/10.2.259"},{"key":"e_1_2_1_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/009841096161898"},{"key":"e_1_2_1_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3835(95)03790-4"},{"key":"e_1_2_1_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/20.10.1885"},{"key":"e_1_2_1_30_1","doi-asserted-by":"publisher","DOI":"10.1080\/08958370304476"},{"key":"e_1_2_1_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/08958370701271373"},{"key":"e_1_2_1_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.20142"},{"key":"e_1_2_1_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/mutage\/geh058"},{"key":"e_1_2_1_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R400004200"},{"key":"e_1_2_1_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2006.08.011"},{"key":"e_1_2_1_36_1","doi-asserted-by":"publisher","DOI":"10.1006\/taap.1998.8525"},{"key":"e_1_2_1_37_1","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0031-6997(25)00051-1","article-title":"Metabolism of polycyclic aromatic hydrocarbons: Etiologic role in carcinogenesis","volume":"34","author":"Pelkonen O","year":"1982","journal-title":"Pharmacol Rev"},{"key":"e_1_2_1_38_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.8142163"},{"key":"e_1_2_1_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205803"},{"key":"e_1_2_1_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(80)90505-9"},{"key":"e_1_2_1_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/9.7.1247"},{"key":"e_1_2_1_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0232-1513(11)80187-8"},{"key":"e_1_2_1_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2005.06.002"},{"key":"e_1_2_1_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2006.02.006"},{"key":"e_1_2_1_45_1","doi-asserted-by":"publisher","DOI":"10.1080\/08958370600686341"},{"key":"e_1_2_1_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/8.8.1145"},{"key":"e_1_2_1_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.19.7499"},{"key":"e_1_2_1_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/18.1.127"},{"key":"e_1_2_1_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041540212"},{"key":"e_1_2_1_50_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.99107s15"},{"key":"e_1_2_1_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1110(77)90020-3"},{"key":"e_1_2_1_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(01)00268-4"},{"key":"e_1_2_1_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.61"},{"key":"e_1_2_1_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002400050068"},{"key":"e_1_2_1_55_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.39.1.103"},{"key":"e_1_2_1_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1383-5718(02)00240-1"},{"key":"e_1_2_1_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0027-5107(96)00213-8"},{"key":"e_1_2_1_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0887-2333(98)00003-4"}],"container-title":["Environmental Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Ftox.20484","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/tox.20484","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,9]],"date-time":"2025-02-09T06:29:20Z","timestamp":1739082560000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/tox.20484"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,4,30]]},"references-count":57,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2010,4]]}},"alternative-id":["10.1002\/tox.20484"],"URL":"https:\/\/doi.org\/10.1002\/tox.20484","archive":["Portico"],"relation":{},"ISSN":["1520-4081","1522-7278"],"issn-type":[{"value":"1520-4081","type":"print"},{"value":"1522-7278","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,4,30]]},"assertion":[{"value":"2008-12-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-02-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-04-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}