An overview of benzene metabolism.

Abstract

Benzene toxicity involves both bone marrow depression and leukemogenesis caused by damage to multiple classes of hematopoietic cells and a variety of hematopoietic cell functions. Study of the relationship between the metabolism and toxicity of benzene indicates that several metabolites of benzene play significant roles in generating benzene toxicity. Benzene is metabolized, primarily in the liver, to a variety of hydroxylated and ring-opened products that are transported to the bone marrow where subsequent secondary metabolism occurs. Two potential mechanisms by which benzene metabolites may damage cellular macromolecules to induce toxicity include the covalent binding of reactive metabolites of benzene and the capacity of benzene metabolites to induce oxidative damage. Although the relative contributions of each of these mechanisms to toxicity remains unestablished, it is clear that different mechanisms contribute to the toxicities associated with different metabolites. As a corollary, it is unlikely that benzene toxicity can be described as the result of the interaction of a single metabolite with a single biological target. Continued investigation of the metabolism of benzene and its metabolites will allow us to determine the specific combination of metabolites as well as the biological target(s) involved in toxicity and will ultimately lead to our understanding of the relationship between the production of benzene metabolites and bone marrow toxicity.

Protective Effect of Vitamins C and E against Gasoline Vapors Induced Haematological and Biochemical Changes in Male Rats

“…It was reported that some of gasoline vapors components are haematotoxic in humans (workers subjected to benzene, toluene and xylene) [15,16] and the same observation was reported in experimental animals (rats exposed to gasoline vapors) [17]. In the present study, gasoline 80 inhalation significantly reduced the PCV in treated male rats.…”

Associations between blood BTEXS concentrations and hematologic parameters among adult residents of the U.S. Gulf States

“…2010; IARC 2011). Briefly, benzene is metabolized to several reactive metabolites that can damage hematopoietic progenitor cells and lead to depression of the bone marrow (Ross 2000; Snyder and Hedli 1996; Wang et al 2012). This hematopoietic damage is upstream of blood cell formation and can manifest as reduced blood cell counts (cytopenia) and altered hematologic parameters, while prolonged exposure can lead to hematologic conditions including aplastic anemia, leukemia, and other hematologic cancers (ATSDR 2007a; Galbraith et al 2010; IARC 2011).…”

The vanishing zero revisited: Thresholds in the age of genomics

“…The mechanism by which benzene induces leukemia is as yet unresolved and remains an area of intensive research [39- 41]. The metabolism of benzene is complex [42], generating numerous DNA reactive intermediates, phenols and quinones that can react with DNA directly, or generate DNA reactive oxygen species [43]. Although the metabolism of benzene to DNA-reactive intermediates is required for leukemogenesis, most of the products produced are weak mutagens per se .…”