Advances in understanding benzene health effects and susceptibility

Abstract

Benzene is a ubiquitous chemical in our environment that causes acute leukemia and probably other hematological cancers. Evidence for an association with childhood leukemia is growing. Exposure to benzene can lead to multiple alterations that contribute to the leukemogenic process, indicating a multimodal mechanism of action. Research is needed to elucidate the different roles of multiple metabolites in benzene toxicity and the pathways that lead to their formation. Studies to date have identified a number of polymorphisms in candidate genes that confer susceptibility to benzene hematotoxicity. However, a genome-wide study is needed to truly assess the role of genetic variation in susceptibility. Benzene affects the blood-forming system at low levels of occupational exposure, and there is no evidence of a threshold. There is probably no safe level of exposure to benzene, and all exposures constitute some risk in a linear, if not supralinear, and additive fashion.

Figure 1

Genetic pathways to myeloid leukemia (adapted from Reference 76).

Figure 2

Simplified metabolic scheme for benzene showing major pathways and metabolizing enzymes leading to toxicity. CYP2E1, cytochrome P450 2E1; GST, glutathione-S-transferase; NQO1, NAD(P)H:quinone oxidoreductase 1; MPO, myeloperoxidase; UDPGT, uridine diphosphate glucuronyl transferase; PST, phenol sulfotransferase; mEH, microsomal epoxide hydrolase.