PMID- 33851706 OWN - NLM STAT- MEDLINE DCOM- 20211022 LR - 20231213 IS - 1470-8736 (Electronic) IS - 0143-5221 (Print) IS - 0143-5221 (Linking) VI - 135 IP - 8 DP - 2021 Apr 30 TI - In utero and early-life exposure to thirdhand smoke causes profound changes to the immune system. PG - 1053-1063 LID - 10.1042/CS20201498 [doi] AB - 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. CI - (c) 2021 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society. FAU - Snijders, Antoine M AU - Snijders AM AD - Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, U.S.A. FAU - Zhou, Mi AU - Zhou M AD - Department of Laboratory Medicine, University of California, San Francisco, CA, U.S.A. FAU - Whitehead, Todd P AU - Whitehead TP AD - School of Public Health, University of California, Berkeley, CA, U.S.A. FAU - Fitch, Briana AU - Fitch B AD - Department of Laboratory Medicine, University of California, San Francisco, CA, U.S.A. FAU - Pandey, Priyatama AU - Pandey P AD - Center for Genetic Epidemiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, U.S.A. FAU - Hechmer, Aaron AU - Hechmer A AD - UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, U.S.A. FAU - Huang, Abel AU - Huang A AD - Division of Occupational and Environmental Medicine, Department of Medicine, University of California, San Francisco, CA, U.S.A. FAU - Schick, Suzaynn F AU - Schick SF AD - UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, U.S.A. AD - Division of Occupational and Environmental Medicine, Department of Medicine, University of California, San Francisco, CA, U.S.A. FAU - de Smith, Adam J AU - de Smith AJ AD - Center for Genetic Epidemiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, U.S.A. FAU - Olshen, Adam B AU - Olshen AB AD - UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, U.S.A. AD - Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, U.S.A. FAU - Metayer, Catherine AU - Metayer C AD - School of Public Health, University of California, Berkeley, CA, U.S.A. FAU - Mao, Jian-Hua AU - Mao JH AD - Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, U.S.A. FAU - Wiemels, Joseph L AU - Wiemels JL AD - Center for Genetic Epidemiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, U.S.A. FAU - Kogan, Scott C AU - Kogan SC AD - Department of Laboratory Medicine, University of California, San Francisco, CA, U.S.A. AD - UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, U.S.A. LA - eng GR - P50 ES018172/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - England TA - Clin Sci (Lond) JT - Clinical science (London, England : 1979) JID - 7905731 RN - 0 (Smoke) RN - 0 (Tobacco Smoke Pollution) SB - IM MH - Animals MH - Immune System/*drug effects MH - Leukemia/*etiology/immunology MH - Lymphoma/*etiology/immunology MH - Mice, Transgenic MH - Smoke/*adverse effects MH - Nicotiana/*adverse effects MH - Tobacco Smoke Pollution/adverse effects/analysis PMC - PMC8086195 MID - NIHMS1698153 OTO - NOTNLM OT - immunology OT - leukemia OT - lymphoma OT - thirdhand smoke COIS- The authors declare that there are no competing interests associated with the manuscript. EDAT- 2021/04/15 06:00 MHDA- 2023/02/25 06:00 PMCR- 2021/04/23 CRDT- 2021/04/14 08:38 PHST- 2020/12/14 00:00 [received] PHST- 2021/04/01 00:00 [revised] PHST- 2021/04/14 00:00 [accepted] PHST- 2021/04/15 06:00 [pubmed] PHST- 2023/02/25 06:00 [medline] PHST- 2021/04/14 08:38 [entrez] PHST- 2021/04/23 00:00 [pmc-release] AID - 228332 [pii] AID - CS20201498 [pii] AID - 10.1042/CS20201498 [doi] PST - ppublish SO - Clin Sci (Lond). 2021 Apr 30;135(8):1053-1063. doi: 10.1042/CS20201498.