Combined exposure to formaldehyde and PM(2.5): Hematopoietic toxicity and molecular mechanism in mice

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.