{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:23:47Z","timestamp":1789431827978,"version":"build-2803163510"},"reference-count":30,"publisher":"Portland Press Ltd.","issue":"8","license":[{"start":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T00:00:00Z","timestamp":1618358400000},"content-version":"vor","delay-in-days":13,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,4,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Thirdhand smoke (THS) is the residual tobacco contamination that remains after the smoke clears. We investigated the effects of THS exposure in utero and during early life in a transgenic Cdkn2a knockout mouse model that is vulnerable to the development of leukemia\/lymphoma. Female mice, and their offspring, were exposed from the first day of pregnancy to weaning. Plasma cytokines, body weight and hematologic parameters were measured in the offspring. To investigate THS exposure effects on the development of leukemia\/lymphoma, bone marrow (BM) was collected from control and THS-exposed mice and transplanted into BM-ablated recipient mice, which were followed for tumor development for 1 year. We found that in utero and early-life THS exposure caused significant changes in plasma cytokine concentrations and in immune cell populations; changes appeared more pronounced in male mice. Spleen (SP) and BM B-cell populations were significantly lower in THS-exposed mice. We furthermore observed that THS exposure increased the leukemia\/lymphoma-free survival in BM transplantation recipient mice, potentially caused by THS-induced B-cell toxicity. A trend towards increased solid tumors in irradiated mice reconstituted with THS-exposed BM stimulates the hypothesis that the immunosuppressive effects of in utero and early-life THS exposure might contribute to carcinogenesis by lowering the host defense to other toxic exposures. Our study adds to expanding evidence that THS exposure alters the immune system and that in utero and early-life developmental periods represent vulnerable windows of susceptibility for these effects.<\/jats:p>","DOI":"10.1042\/cs20201498","type":"journal-article","created":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T01:17:38Z","timestamp":1618535858000},"page":"1053-1063","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["<i>In utero<\/i> and early-life exposure to thirdhand smoke causes profound changes to the immune system"],"prefix":"10.1042","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7086-1063","authenticated-orcid":false,"given":"Antoine\u00a0M.","family":"Snijders","sequence":"first","affiliation":[{"name":"Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of California, San Francisco, CA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd\u00a0P.","family":"Whitehead","sequence":"additional","affiliation":[{"name":"School of Public Health, University of California, Berkeley, CA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Briana","family":"Fitch","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of California, San Francisco, CA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyatama","family":"Pandey","sequence":"additional","affiliation":[{"name":"Center for Genetic Epidemiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Hechmer","sequence":"additional","affiliation":[{"name":"UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abel","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Occupational and Environmental Medicine, Department of Medicine, University of California, San Francisco, CA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzaynn\u00a0F.","family":"Schick","sequence":"additional","affiliation":[{"name":"UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, U.S.A."},{"name":"Division of Occupational and Environmental Medicine, Department of Medicine, University of California, San Francisco, CA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam\u00a0J.","family":"de Smith","sequence":"additional","affiliation":[{"name":"Center for Genetic Epidemiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam\u00a0B.","family":"Olshen","sequence":"additional","affiliation":[{"name":"UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, U.S.A."},{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Metayer","sequence":"additional","affiliation":[{"name":"School of Public Health, University of California, Berkeley, CA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Hua","family":"Mao","sequence":"additional","affiliation":[{"name":"Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph\u00a0L.","family":"Wiemels","sequence":"additional","affiliation":[{"name":"Center for Genetic Epidemiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2395-8479","authenticated-orcid":false,"given":"Scott\u00a0C.","family":"Kogan","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of California, San Francisco, CA, U.S.A."},{"name":"UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2021,4,23]]},"reference":[{"key":"2021113011205123100_B1","doi-asserted-by":"publisher","first-page":"1000","DOI":"10.1002\/ijc.30487","article-title":"Trends in childhood leukemia incidence over two decades from 1992 to 2013","volume":"140","author":"Barrington-Trimis","year":"2017","journal-title":"Int. J. Cancer"},{"key":"2021113011205123100_B2","doi-asserted-by":"publisher","first-page":"2371","DOI":"10.1001\/jama.2013.6296","article-title":"Clinical ascertainment of health outcomes among adults treated for childhood cancer","volume":"309","author":"Hudson","year":"2013","journal-title":"JAMA"},{"key":"2021113011205123100_B3","doi-asserted-by":"publisher","first-page":"1572","DOI":"10.1056\/NEJMsa060185","article-title":"Chronic health conditions in adult survivors of childhood cancer","volume":"355","author":"Oeffinger","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"2021113011205123100_B4","doi-asserted-by":"publisher","first-page":"3033","DOI":"10.1182\/blood-2015-03-634006","article-title":"Rising rates of acute lymphoblastic leukemia in Hispanic children: trends in incidence from 1992 to 2011","volume":"125","author":"Barrington-Trimis","year":"2015","journal-title":"Blood"},{"key":"2021113011205123100_B5","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.cppeds.2016.08.004","article-title":"Childhood leukemia and primary prevention","volume":"46","author":"Whitehead","year":"2016","journal-title":"Curr. Probl. Pediatr. Adolesc. Health Care"},{"key":"2021113011205123100_B6","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1038\/s41568-018-0015-6","article-title":"A causal mechanism for childhood acute lymphoblastic leukaemia","volume":"18","author":"Greaves","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"2021113011205123100_B7","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1136\/thx.2010.153379","article-title":"Exposure to parental and sibling smoking and the risk of smoking uptake in childhood and adolescence: a systematic review and meta-analysis","volume":"66","author":"Leonardi-Bee","year":"2011","journal-title":"Thorax"},{"key":"2021113011205123100_B8","doi-asserted-by":"publisher","first-page":"105833","DOI":"10.1016\/j.ypmed.2019.105833","article-title":"Burden of disease attributable to second-hand smoke exposure: a systematic review","volume":"129","author":"Carreras","year":"2019","journal-title":"Prev. Med."},{"key":"2021113011205123100_B9","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1289\/ehp.1103500","article-title":"Thirdhand tobacco smoke: emerging evidence and arguments for a multidisciplinary research agenda","volume":"119","author":"Matt","year":"2011","journal-title":"Environ. Health Perspect."},{"key":"2021113011205123100_B10","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1021\/acs.chemrestox.6b00343","article-title":"Thirdhand smoke: new evidence, challenges, and future directions","volume":"30","author":"Jacob","year":"2017","journal-title":"Chem. Res. Toxicol."},{"key":"2021113011205123100_B11","doi-asserted-by":"publisher","first-page":"e74","DOI":"10.1542\/peds.2008-2184","article-title":"Beliefs about the health effects of \u201cthirdhand\u201d smoke and home smoking bans","volume":"123","author":"Winickoff","year":"2009","journal-title":"Pediatrics"},{"key":"2021113011205123100_B12","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1093\/ntr\/ntt014","article-title":"Wipe sampling for nicotine as a marker of thirdhand tobacco smoke contamination on surfaces in homes, cars, and hotels","volume":"15","author":"Quintana","year":"2013","journal-title":"Nicotine Tob. Res."},{"key":"2021113011205123100_B13","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1136\/tobaccocontrol-2012-050824","article-title":"Thirdhand smoke and exposure in California hotels: non-smoking rooms fail to protect non-smoking hotel guests from tobacco smoke exposure","volume":"23","author":"Matt","year":"2014","journal-title":"Tob. Control"},{"key":"2021113011205123100_B14","doi-asserted-by":"publisher","first-page":"2409","DOI":"10.1042\/CS20171053","article-title":"Biomarkers of disease can be detected in mice as early as 4 weeks after initiation of exposure to third-hand smoke levels equivalent to those found in homes of smokers","volume":"131","author":"Adhami","year":"2017","journal-title":"Clin. Sci. (Lond.)"},{"key":"2021113011205123100_B15","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.fct.2018.09.048","article-title":"Biological markers of harm can be detected in mice exposed for two months to low doses of Third Hand Smoke under conditions that mimic human exposure","volume":"122","author":"Chen","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"2021113011205123100_B16","doi-asserted-by":"publisher","first-page":"41915","DOI":"10.1038\/srep41915","article-title":"Early exposure to thirdhand cigarette smoke affects body mass and the development of immunity in mice","volume":"7","author":"Hang","year":"2017","journal-title":"Sci. Rep."},{"key":"2021113011205123100_B17","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1038\/nature05690","article-title":"Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia","volume":"446","author":"Mullighan","year":"2007","journal-title":"Nature"},{"key":"2021113011205123100_B18","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1038\/leu.2013.15","article-title":"Initially disadvantaged, TEL-AML1 cells expand and initiate leukemia in response to irradiation and cooperating mutations","volume":"27","author":"Li","year":"2013","journal-title":"Leukemia"},{"key":"2021113011205123100_B19","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/S0092-8674(00)81079-X","article-title":"Role of the INK4a locus in tumor suppression and cell mortality","volume":"85","author":"Serrano","year":"1996","journal-title":"Cell"},{"key":"2021113011205123100_B20","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1042\/CS20171521","article-title":"Short-term early exposure to thirdhand cigarette smoke increases lung cancer incidence in mice","volume":"132","author":"Hang","year":"2018","journal-title":"Clin. Sci. (Lond.)"},{"key":"2021113011205123100_B21","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/sj.bmt.1705727","article-title":"Competing risk analysis using R: an easy guide for clinicians","volume":"40","author":"Scrucca","year":"2007","journal-title":"Bone Marrow Transplant."},{"key":"2021113011205123100_B22","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1097\/EDE.0000000000000911","article-title":"Parental smoking and risk of childhood-onset type 1 diabetes","volume":"29","author":"Magnus","year":"2018","journal-title":"Epidemiology"},{"key":"2021113011205123100_B23","doi-asserted-by":"publisher","first-page":"74","DOI":"10.3389\/fimmu.2018.00074","article-title":"Impact of cigarette smoking on the gastrointestinal tract inflammation: opposing effects in Crohn\u2019s disease and ulcerative colitis","volume":"9","author":"Berkowitz","year":"2018","journal-title":"Front. Immunol."},{"key":"2021113011205123100_B24","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.1164\/rccm.200909-1338OC","article-title":"Smoking, use of moist snuff, and risk of chronic inflammatory diseases","volume":"181","author":"Carlens","year":"2010","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2021113011205123100_B25","doi-asserted-by":"publisher","first-page":"1904","DOI":"10.1001\/jama.1986.03370140102032","article-title":"The relation of endometriosis to menstrual characteristics, smoking, and exercise","volume":"255","author":"Cramer","year":"1986","journal-title":"JAMA"},{"key":"2021113011205123100_B26","first-page":"912","article-title":"Exploring causality of the association between smoking and Parkinson\u2019s disease","volume":"48","author":"Gallo","year":"2019","journal-title":"Int. J. Epidemiol."},{"key":"2021113011205123100_B27","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1038\/nri803","article-title":"Effects of cigarette smoke on the immune system","volume":"2","author":"Sopori","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"2021113011205123100_B28","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/s12931-017-0591-0","article-title":"Sex-specific lung functional changes in adult mice exposed only to second-hand smoke in utero","volume":"18","author":"Noel","year":"2017","journal-title":"Respir. Res."},{"key":"2021113011205123100_B29","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1165\/rcmb.2013-0164OC","article-title":"In utero exposure to second-hand smoke aggravates the response to ovalbumin in adult mice","volume":"49","author":"Xiao","year":"2013","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2021113011205123100_B30","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1038\/ng1104-1133","article-title":"The Collaborative Cross, a community resource for the genetic analysis of complex traits","volume":"36","author":"Churchill","year":"2004","journal-title":"Nat. Genet."}],"container-title":["Clinical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/135\/8\/1053\/909002\/cs-2020-1498.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/135\/8\/1053\/909002\/cs-2020-1498.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T12:17:46Z","timestamp":1638274666000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/clinsci\/article\/135\/8\/1053\/228332\/In-utero-and-early-life-exposure-to-thirdhand"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4]]},"references-count":30,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2021,4,30]]}},"URL":"https:\/\/doi.org\/10.1042\/cs20201498","relation":{},"ISSN":["0143-5221","1470-8736"],"issn-type":[{"value":"0143-5221","type":"print"},{"value":"1470-8736","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,4]]},"published":{"date-parts":[[2021,4]]}}}