Types of hematologic responses to benzene:
(1) lymphocytopenia
(2) thrombocytopenia
(3) leukopenia
(4) anemia
(5) pancytopenia
(6) aplastic anemia
(7) myelodysplasia
(8) acute myelogenous leukemia
Proposed mechanisms for myelotoxicity:
(1) interference with DNA synthesis
(2) interference with microtubule or spindle formation
Possible targets of active metabolites:
(1) stem cells
(2) bone marrow stromal cells
Risk factors for myelotoxicity:
(1) chronic exposure to high levels of benzene
(2) folic acid deficiency
(3) metabolic imbalance (increased peroxidation, reduced deactivation) resulting in overproduction of an active metabolite (possibly hydroquinone, others)
where:
• Activity of myeloperoxidase results in activation of benzene. NAD(P)H:quinone acceptor oxidoreductase (NQO1) reverses the activation.
• Smith linked susceptibility in some patients to increased P450 2E1 activity in the liver.
• The metabolic imbalance may be due to enzyme polymorphism, induction or inhibition.
