{"title":"4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK).","authors":"Xinxin Ding, Xin Zhou","doi":"10.1158/1538-7445.AM2011-3236","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2011-3236","url":null,"abstract":"Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL\u0000\u0000NNK is a potent lung procarcinogen. Previously, we have demonstrated that NNK-induced lung tumorigenesis depends on target-tissue metabolic activation by pulmonary P450 enzymes. The aim of this study is to test the hypotheses that 1) mouse CYP2A5 plays an essential role in NNK bioactivation in the lung, and 2) transgenic expression of human CYP2A13, known to be selectively expressed in the respiratory tract, and be the most efficient enzyme for NNK metabolic activation in vitro, can increase the rates of NNK metabolic activation in the mouse lung. We determined the rates of in vitro formation of 4-oxo-4-(3-pyridyl)-butanal (OPB), representing the reactive intermediate that can lead to the further formation of O6-mehtylguanine (O6-mG) DNA adduct, in liver and lung microsomes of wild-type, Cyp2a5-null, and CYP2A13-humanized (CYP2A13-transgenic/Cyp2a5-null) mice. We found that, in both liver and lung microsomes, the loss of CYP2A5 resulted in significant decreases in the rates of formation of OPB; whereas, the gain of CYP2A13 led to recovery of the microsomal activity in the lung, but not in the liver. Furthermore, we observed that the levels of O6-mG, the DNA adduct known to be most highly correlated with incidences of lung tumor formation, were significantly higher in the lungs of the CYP2A13-humanized mice, than in the Cyp2a5-null mice. In control experiments, rates of systemic clearance of NNK and its major circulating metabolite, NNAL, were confirmed to be not different among the three mouse strains. These results indicate that CYP2A13 can catalyze NNK bioactivation in vivo, and they support the idea that CYP2A13 genetic polymorphisms can influence the risks of tobacco-induced lung tumorigenesis in humans. (Supported in part by NIH grant CA092596)\u0000\u0000Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3236. doi:10.1158/1538-7445.AM2011-3236","PeriodicalId":75918,"journal":{"name":"IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans","volume":"37 1","pages":"209-23"},"PeriodicalIF":0.0,"publicationDate":"2011-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64320910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sample Preparation Techniques for Environmental Organic Pollutant Analysis","authors":"R. Clement, C. Hao","doi":"10.1002/9780813823621.CH14","DOIUrl":"https://doi.org/10.1002/9780813823621.CH14","url":null,"abstract":"","PeriodicalId":75918,"journal":{"name":"IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans","volume":"36 1","pages":"247-265"},"PeriodicalIF":0.0,"publicationDate":"2011-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/9780813823621.CH14","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50700613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Benzo[ghi]perylene.","authors":"J. Montgomery","doi":"10.1201/9781420009132-38","DOIUrl":"https://doi.org/10.1201/9781420009132-38","url":null,"abstract":"","PeriodicalId":75918,"journal":{"name":"IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans","volume":"32 1","pages":"195-204"},"PeriodicalIF":0.0,"publicationDate":"2007-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65960249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Benzo[k]fluoranthene.","authors":"John Montgomery","doi":"10.1201/9781420009132-36","DOIUrl":"https://doi.org/10.1201/9781420009132-36","url":null,"abstract":"A pale yellow aromatic hydrocarbon consisting of five fused rings and is produced by the incomplete combustion of organic matter. Benzo(k)fluoranthene is primarily found in gasoline exhaust, cigarette smoke, coal tar, coal and oil combustion emissions, lubricating oils, used motor oils and crude oils. T his substance is used only for research purposes. Benzo(k)fluoranthene is reasonably anticipated to be a human carcinogen. (NCI05) Qeios · Definition, February 7, 2020","PeriodicalId":75918,"journal":{"name":"IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans","volume":"32 1","pages":"163-70"},"PeriodicalIF":0.0,"publicationDate":"2007-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65960331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Indeno [1,2,3-cd]pyrene.","authors":"J. Montgomery","doi":"10.1002/9780470114735.hawley08876","DOIUrl":"https://doi.org/10.1002/9780470114735.hawley08876","url":null,"abstract":"A yellowish, aromatic hydrocarbon consisting of six fused rings and produced by the incomplete combustion of organic matter. Indene[1,2,3-cd]pyrene is primarily found in certain foods, gasoline and diesel exhaust, cigarette smoke, coal tar and coal tar pitch, soot and petroleum asphalt. T his substance is used only for research purposes. Indene[1,2,3-cd]pyrene is reasonably anticipated to be a human carcinogen. (NCI05) Qeios · Definition, February 7, 2020","PeriodicalId":75918,"journal":{"name":"IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans","volume":"32 1","pages":"373-8"},"PeriodicalIF":0.0,"publicationDate":"2007-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"51145381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Attapulgite.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":75918,"journal":{"name":"IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans","volume":"42 ","pages":"159-73"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14443211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sepiolite.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":75918,"journal":{"name":"IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans","volume":"42 ","pages":"175-83"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14095454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Silica and some silicates.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":75918,"journal":{"name":"IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans","volume":"42 ","pages":"1-239"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13962533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Erionite.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":75918,"journal":{"name":"IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans","volume":"42 ","pages":"225-39"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13962535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Wollastonite.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":75918,"journal":{"name":"IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans","volume":"42 ","pages":"145-58"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13962534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}