Combined exposure to formaldehyde and PM2.5: Hematopoietic toxicity and molecular mechanism in mice
PM2.5 and formaldehyde (FA) are major outdoor and indoor air pollutants in China, respectively, and both are known to be harmful to human health and to be carcinogenic. Of all the known chronic health effects, leukaemia is one of the most serious health risks associated with these two pollutants. To...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-11-01
|
| Series: | Environment International |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412020320055 |
| _version_ | 1818570337106788352 |
|---|---|
| author | Jing Ge Honglian Yang Xianxian Lu Shenqi Wang Yun Zhao Jiawei Huang Zhuge Xi Luoping Zhang Rui Li |
| author_facet | Jing Ge Honglian Yang Xianxian Lu Shenqi Wang Yun Zhao Jiawei Huang Zhuge Xi Luoping Zhang Rui Li |
| author_sort | Jing Ge |
| collection | DOAJ |
| description | PM2.5 and formaldehyde (FA) are major outdoor and indoor air pollutants in China, respectively, and both are known to be harmful to human health and to be carcinogenic. Of all the known chronic health effects, leukaemia is one of the most serious health risks associated with these two pollutants. To explore the influence and underlying mechanisms of exposure to formaldehyde and PM2.5 on hematopoietic toxicity, we systematically studied the toxicity induced in hematopoietic organs: bone marrow (BM); spleen; and myeloid progenitor cells (MPCs). Male Balb/c mice were exposed to: PM2.5 (20, 160 μg/kg·d) at a dose of 40 μL per mouse or formaldehyde (0.5, 3.0 mg/m3) for 8 h per day for 2 weeks or co-exposed to formaldehyde and PM2.5 (20 μg/kg·d PM2.5 + 0.5 mg/m3 FA, 20 μg/kg·d PM2.5 + 3 mg/m3 FA, 160 μg/kg·d PM2.5 + 0.5 mg/m3 FA, 160 μg/kg·d PM2.5 + 3 mg/m3 FA) for 2 weeks. Similar toxic effects were found in the formaldehyde-only and PM2.5-only groups, including significant decrease of blood cells and MPCs, along with decreased expression of hematopoietic growth factors. In addition, individual exposure of formaldehyde or PM2.5 increased oxidative stress, DNA damage and immune system disorder by destroying the balance of Th1/Th2, and Treg/Th17. DNA repair was markedly inhibited by deregulating the mammalian target of rapamycin (mTOR) pathway. Combined exposure to PM2.5 and formaldehyde led to more severe effects. Administration of Vitamin E (VE) was shown to attenuate these effects. In conclusion, our findings suggested that PM2.5 and formaldehyde may induce hematopoietic toxicity by reducing the expression of hematopoietic growth factors, increasing oxidative stress and DNA damage, activating the ‘immune imbalance’ pathway and suppressing the DNA-repair related mTOR pathway. The hematopoietic toxicity induced by combined exposure of PM2.5 and formaldehyde might provide further insights into the increased incidence of hematological diseases, including human myeloid leukaemia. |
| first_indexed | 2024-12-14T12:59:24Z |
| format | Article |
| id | doaj.art-e3064afba8304044a3e86a3d9c171ef2 |
| institution | Directory Open Access Journal |
| issn | 0160-4120 |
| language | English |
| last_indexed | 2024-12-14T12:59:24Z |
| publishDate | 2020-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Environment International |
| spelling | doaj.art-e3064afba8304044a3e86a3d9c171ef22022-12-21T23:00:30ZengElsevierEnvironment International0160-41202020-11-01144106050Combined exposure to formaldehyde and PM2.5: Hematopoietic toxicity and molecular mechanism in miceJing Ge0Honglian Yang1Xianxian Lu2Shenqi Wang3Yun Zhao4Jiawei Huang5Zhuge Xi6Luoping Zhang7Rui Li8Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, China; College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, ChinaTianjin Institute of Environmental and Operational Medicine, Tianjin 300050, ChinaHubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, ChinaCollege of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, ChinaHubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, ChinaHubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, ChinaTianjin Institute of Environmental and Operational Medicine, Tianjin 300050, ChinaDivision of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA 94720, USA; Corresponding authors.Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, China; Corresponding authors.PM2.5 and formaldehyde (FA) are major outdoor and indoor air pollutants in China, respectively, and both are known to be harmful to human health and to be carcinogenic. Of all the known chronic health effects, leukaemia is one of the most serious health risks associated with these two pollutants. To explore the influence and underlying mechanisms of exposure to formaldehyde and PM2.5 on hematopoietic toxicity, we systematically studied the toxicity induced in hematopoietic organs: bone marrow (BM); spleen; and myeloid progenitor cells (MPCs). Male Balb/c mice were exposed to: PM2.5 (20, 160 μg/kg·d) at a dose of 40 μL per mouse or formaldehyde (0.5, 3.0 mg/m3) for 8 h per day for 2 weeks or co-exposed to formaldehyde and PM2.5 (20 μg/kg·d PM2.5 + 0.5 mg/m3 FA, 20 μg/kg·d PM2.5 + 3 mg/m3 FA, 160 μg/kg·d PM2.5 + 0.5 mg/m3 FA, 160 μg/kg·d PM2.5 + 3 mg/m3 FA) for 2 weeks. Similar toxic effects were found in the formaldehyde-only and PM2.5-only groups, including significant decrease of blood cells and MPCs, along with decreased expression of hematopoietic growth factors. In addition, individual exposure of formaldehyde or PM2.5 increased oxidative stress, DNA damage and immune system disorder by destroying the balance of Th1/Th2, and Treg/Th17. DNA repair was markedly inhibited by deregulating the mammalian target of rapamycin (mTOR) pathway. Combined exposure to PM2.5 and formaldehyde led to more severe effects. Administration of Vitamin E (VE) was shown to attenuate these effects. In conclusion, our findings suggested that PM2.5 and formaldehyde may induce hematopoietic toxicity by reducing the expression of hematopoietic growth factors, increasing oxidative stress and DNA damage, activating the ‘immune imbalance’ pathway and suppressing the DNA-repair related mTOR pathway. The hematopoietic toxicity induced by combined exposure of PM2.5 and formaldehyde might provide further insights into the increased incidence of hematological diseases, including human myeloid leukaemia.http://www.sciencedirect.com/science/article/pii/S0160412020320055PM2.5FormaldehydeCombined exposureHematopoietic toxicityMolecular mechanism |
| spellingShingle | Jing Ge Honglian Yang Xianxian Lu Shenqi Wang Yun Zhao Jiawei Huang Zhuge Xi Luoping Zhang Rui Li Combined exposure to formaldehyde and PM2.5: Hematopoietic toxicity and molecular mechanism in mice Environment International PM2.5 Formaldehyde Combined exposure Hematopoietic toxicity Molecular mechanism |
| title | Combined exposure to formaldehyde and PM2.5: Hematopoietic toxicity and molecular mechanism in mice |
| title_full | Combined exposure to formaldehyde and PM2.5: Hematopoietic toxicity and molecular mechanism in mice |
| title_fullStr | Combined exposure to formaldehyde and PM2.5: Hematopoietic toxicity and molecular mechanism in mice |
| title_full_unstemmed | Combined exposure to formaldehyde and PM2.5: Hematopoietic toxicity and molecular mechanism in mice |
| title_short | Combined exposure to formaldehyde and PM2.5: Hematopoietic toxicity and molecular mechanism in mice |
| title_sort | combined exposure to formaldehyde and pm2 5 hematopoietic toxicity and molecular mechanism in mice |
| topic | PM2.5 Formaldehyde Combined exposure Hematopoietic toxicity Molecular mechanism |
| url | http://www.sciencedirect.com/science/article/pii/S0160412020320055 |
| work_keys_str_mv | AT jingge combinedexposuretoformaldehydeandpm25hematopoietictoxicityandmolecularmechanisminmice AT honglianyang combinedexposuretoformaldehydeandpm25hematopoietictoxicityandmolecularmechanisminmice AT xianxianlu combinedexposuretoformaldehydeandpm25hematopoietictoxicityandmolecularmechanisminmice AT shenqiwang combinedexposuretoformaldehydeandpm25hematopoietictoxicityandmolecularmechanisminmice AT yunzhao combinedexposuretoformaldehydeandpm25hematopoietictoxicityandmolecularmechanisminmice AT jiaweihuang combinedexposuretoformaldehydeandpm25hematopoietictoxicityandmolecularmechanisminmice AT zhugexi combinedexposuretoformaldehydeandpm25hematopoietictoxicityandmolecularmechanisminmice AT luopingzhang combinedexposuretoformaldehydeandpm25hematopoietictoxicityandmolecularmechanisminmice AT ruili combinedexposuretoformaldehydeandpm25hematopoietictoxicityandmolecularmechanisminmice |