{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T09:41:57Z","timestamp":1789810917363,"version":"4.0.1"},"reference-count":102,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T00:00:00Z","timestamp":1709510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000030","name":"US Centers for Disease Control and Prevention","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000030","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The tobacco-specific nitrosamines N\u02b9-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are considered \u2018carcinogenic to humans\u2019 by the International Agency for Research on Cancer (IARC) and are believed to be important in the carcinogenic effects of both smokeless tobacco and combusted tobacco products. This short review focuses on the results of recent studies on the formation of NNN and NNK in tobacco, and their carcinogenicity and toxicity in laboratory animals. New mechanistic insights are presented regarding the role of dissimilatory nitrate reductases in certain microorganisms involved in the conversion of nitrate to nitrite that leads to the formation of NNN and NNK during curing and processing of tobacco. Carcinogenicity studies of the enantiomers of the major NNK metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and the enantiomers of NNN are reviewed. Recent toxicity studies of inhaled NNK and co-administration studies of NNK with formaldehyde, acetaldehyde, acrolein and CO2, all of which occur in high concentrations in cigarette smoke, are discussed.<\/jats:p>","DOI":"10.1093\/carcin\/bgae018","type":"journal-article","created":{"date-parts":[[2024,3,2]],"date-time":"2024-03-02T01:25:44Z","timestamp":1709342744000},"page":"275-287","source":"Crossref","is-referenced-by-count":30,"title":["An update on the formation in tobacco, toxicity and carcinogenicity of\n                    <i>N<\/i>\n                    \u02b9-nitrosonornicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone"],"prefix":"10.1093","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8715-4480","authenticated-orcid":false,"given":"Lisa A","family":"Peterson","sequence":"first","affiliation":[{"name":"Masonic Cancer Center, University of Minnesota , Minneapolis, MN , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen B","family":"Stanfill","sequence":"additional","affiliation":[{"name":"Tobacco and Volatiles Branch, National Center for Environmental Health, Centers for Disease Control and Prevention , Atlanta, GA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7228-1356","authenticated-orcid":false,"given":"Stephen S","family":"Hecht","sequence":"additional","affiliation":[{"name":"Masonic Cancer Center, University of Minnesota , Minneapolis, MN , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,3,4]]},"reference":[{"key":"2024051916061556900_CIT0001","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1126\/science.186.4160.265","article-title":"N\u02b9-Nitrosonornicotine in tobacco","volume":"186","author":"Hoffmann","year":"1974","journal-title":"Science"},{"key":"2024051916061556900_CIT0002","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1021\/jo00395a017","article-title":"Reaction of nicotine and sodium nitrite: formation of nitrosamines and fragmentation of the pyrrolidine ring","volume":"43","author":"Hecht","year":"1978","journal-title":"J. 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