In utero and early-life exposure to thirdhand smoke causes profound changes to the immune system

Abstract

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 was collected from control and THS-exposed mice and transplanted into bone-marrow-ablated recipient mice, which were followed for tumor development for one 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 and bone marrow B-cell populations were significantly lower in THS-exposed mice. We furthermore observed that THS exposure increased the leukemia/lymphoma-free survival in bone marrow transplantation recipient mice, potentially caused by THS-induced B cell toxicity. A trend towards increased solid tumors in irradiated mice reconstituted with THS exposed bone marrow 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.

Emerging investigator series: deposited particles and human lung lining fluid are dynamic, chemically-complex reservoirs leading to thirdhand smoke emissions and exposure

“…, TSNAs). 1,4,14,80–85 The results of this study expand the scope of identified THS components whose direct effects and secondary transformation products will help to elucidate observed THS health effects and evaluate chemically-speciated contributions to health effects estimates.…”

“…The multi-faceted health effects of THS have been explored and reported across a number of publications for both exposure to real THS (e.g., animal trials with THS exposure, human cohort studies) and by estimating effects from exposure to a subset of previously-known THS components (e.g., acrolein) and select transformation products (e.g., TSNAs). 1,4,14,[80][81][82][83][84][85] The results of this study expand the scope of identied THS components whose direct effects and secondary transformation products will help to elucidate observed THS health effects and evaluate chemicallyspeciated contributions to health effects estimates.…”

Handwashing Results in Incomplete Nicotine Removal from Fingers of Individuals who Smoke: A Randomized Controlled Experiment

“…27 55 56 57 58 59 60 For infants cared for or visited by individuals who smoke, limiting THS exposure from caregivers' hands to infants' skin through increased glove use and/or frequent and rigorous HW are potential paths to mitigate this exposure route. Limiting THS exposure may help reduce alterations in the immune system 59 and gut microbiome 27 for preterm and other vulnerable infants and children in hospital settings exposed to nicotine early in life. Future studies with larger samples, different approaches (e.g., measuring nicotine on the entire hand 4 28 ), and additional cleaning and barrier methods being evaluated will improve on our methods.…”

Implications of the Immune Landscape in COPD and Lung Cancer: Smoking Versus Other Causes

“…Presumably this is due to the assumption that the changes are very similar to those caused by active smoking. One mouse study investigated in utero and early-life passive smoke exposure, and the resulting immunologic changes ( 232 ). Changes in plasma cytokine concentrations and in immune cell populations, i.e.…”

“…decreased percentages of B-cells and increased percentages of myeloid cells were observed in the bone marrow of smoke-exposed versus control mice. In the spleen of passive smoke exposed mice, the abundance of B-cells decreased and that of T-cells increased, whereas myeloid cells were significantly lower in the peripheral blood in smoke exposed mice ( 232 ). The authors of this study conclude that the immune changes resulting from second-hand smoke in utero and in early life are particularly threatening, contributing to carcinogenesis by lowering host defense mechanisms.…”