Combined exposure to formaldehyde and PM2.5: Hematopoietic toxicity and molecular mechanism in mice

Abstract

PM 2.5 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 PM 2.5 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: PM 2.5 (20, 160 μg/kg·d) at a dose of 40 μL per mouse or formaldehyde (0.5, 3.0 mg/m 3 ) for 8 h per day for 2 weeks or co-exposed to formaldehyde and PM 2.5 (20 μg/kg·d PM 2.5 + 0.5 mg/m 3 FA, 20 μ/kg·d PM 2.5 + 3 mg/m 3 FA, 160 μg/kg·d PM 2.5 + 0.5 mg/m 3 FA, 160 μg/kg·d PM 2.5 + 3 mg/m 3 FA) for 2 weeks. Similar toxic effects were found in the formaldehyde-only and PM 2.5 -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 PM 2.5 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 PM 2.5 and formaldehyde led to more severe effects. Administration of Vitamin E (VE) was shown to attenuate these effects. In conclusion, our findings suggested that PM 2.5 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 PM 2.5 and formaldehyde might provide further insights into the increased incidence of hematological diseases, including human myeloid leukaemia.

Particulate Matter and Its Components Induce Alteration on the T-Cell Response: A Population Biomarker Study

“…A study on mice found that PM 2.5 could induce epithelial damage and inflammatory cell infiltration, and there was an imbalance of Th1/Th2 . A research also found increased immune system disorder with the destroyed balance of Th1/Th2 in PM 2.5 -treated mice . In our study, the results showed that T-bet and GATA3 expression had a negative correlation with PM 2.5 exposure.…”

“…15 A research also found increased immune system disorder with the destroyed balance of Th1/Th2 in PM 2.5 -treated mice. 37 In our study, the results showed that T-bet and GATA3 expression had a negative correlation with PM 2.5 exposure. Our results indicated that with the PM increasing, the Th1 expression was more inhibited than Th2.…”

A comprehensive understanding of ambient particulate matter and its components on the adverse health effects based from epidemiological and laboratory evidence

“…It has been suggested that PM 2.5 and formaldehyde might induce hematopoietic toxicity by reducing the expression of blood cells, myeloid progenitor cells (MPCs) and hematopoietic growth factors. In addition, PM 2.5 increased DNA damage and oxidative stress by disrupting the balance of Treg/Th17 and Th1/Th2 and suppressing the DNA-repair related mTOR pathway [ 194 ].…”

Effects of Sanitizers on Microbiological Control of Hatching Eggshells and Poultry Health during Embryogenesis and Early Stages after Hatching in the Last Decade

“…Nevertheless, it is also associated with reports of toxicity and permanent harmful damage to embryos and chicks when applied to hatching eggs ( Table 1 ). Although these effects depend on the concentration, length of time and method of application of formaldehyde and the period in which the egg is exposed [ 13 ], formaldehyde itself is carcinogenic because it impairs and inhibits DNA repair [ 30 ]. Therefore, its use is unjustifiable regarding embryonic life safety, health and protection.…”