Abstract
Benzene is an occupational toxicant and an environmental pollutant that potentially causes hematotoxicity and leukemia in exposed populations. Epidemiological studies suggest an association between an increased incidence of childhood leukemia and benzene exposure during the early stages of pregnancy. However, experimental evidence supporting the association is lacking at the present time. It is believed that benzene and its metabolites target hematopoietic stem cells (HSCs) to cause toxicity and cancer in the hematopoietic system. In the current study, we compared the effects of hydroquinone (HQ), a major metabolite of benzene in humans and animals, on mouse embryonic yolk sac hematopoietic stem cells (YS-HSCs) and adult bone marrow hematopoietic stem cells (BM-HSCs). YS-HSCs and BM-HSCs were isolated and enriched, and were exposed to HQ at increasing concentrations. HQ reduced the proliferation and the differentiation and colony formation, but increased the apoptosis of both YS-HSCs and BM-HSCs. However, the cytotoxic and apoptotic effects of HQ were more apparent and reduction of colony formation by HQ was more severe in YS-HSCs than in BM-HSCs. Differences in gene expression profiles were observed in HQ-treated YS-HSCs and BM-HSCs. Cyp4f18 was induced by HQ both in YS-HSCs and BM-HSCs, whereas DNA-PKcs was induced in BM-HSCs only. The results revealed differential effects of benzene metabolites on embryonic and adult HSCs. The study established an experimental system for comparison of the hematopoietic toxicity and leukemogenicity of benzene and metabolites during mouse embryonic development and adulthood.
Highlights
Benzene is the simplest aromatic compound and is widely used in industrial and chemical manufacturing
The experiment was based on the assumption that, in children with leukemia, oncogenic lesions of the hematopoietic system began to appear during the fetal development and were accumulated as a continuation of the pregnancy, which results in the development of leukemia after birth
It has been demonstrated that YS-hematopoietic stem cells (HSCs) have lymphoid, myeloid and erythroid precusor potentials [40,41,42]
Summary
Benzene is the simplest aromatic compound and is widely used in industrial and chemical manufacturing. High-levels of exposure to benzene results in an increased risk of aplastic anemia, pancytopenia, acute myeloid leukemia, and other forms of leukemia in adults [3,4,5,6]. Childhood leukemia is a major form of cancer in children that develops in the hematopoietic system and is characterized with the production of large amounts of immature white blood cells. Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer worldwide. The mean annual leukemia incidence per million children is 16.4 in low-income countries, 36.5 in middle-income countries, and 40.9 in high-income countries [7]. The cause and oncogenic development of childhood leukemia and why the incidence increases is largely unknown at the present time
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