Leukemia benzene-induced

Crump KS Risk of benzene-induced leukemia a sensitivity analysis of the pliofilm cohort with additional follow-up and new exposure estimates. J Toxicol Environ Health 42 219-242, 1994... 

Subjects with benzene-induced hyporegenerative anemia or pancytopenia of a long-standing duration subsequently developed acute leukemia. Between 1942 and 1975, 66 cases of benzene hemopathy were seen at the Institute of Occupational Health in Milan, Italy (11 of these were leukemia) (Vigliani and Fomi 1976). The affected individuals worked in rotogravure plants, shoe factories, and other industries where benzene was used as a solvent. Benzene concentrations in the air near rotogravure machines were calculated to range between 200 and 400 ppm, with peaks up to 1,500 ppm. 

Experimental data in animals and studies of human cases of benzene intoxication indicate a link between the decrease in bone marrow cellularity and the development of leukemia. Many cases of benzene-induced leukemia appear to have been preceded by aplastic anemia (Toft et al. 1982). The compensatory response (regenerative hyperplasia) observed in the bone marrow, thymus, and spleen of exposed animals may play a role in the carcinogenic response (Rozen and Snyder 1985 Snyder 1987 Snyder and Koscis 1975 Snyder etal. 1984). 

The ultimate mechanism for benzene-induced suppression of cellular growth and the development of leukemia is not known at this time it could be one of the mechanisms discussed above (see also Section 2.4.2) but most likely the mechanism involves a combination of factors. Identification of the mechanism would be facilitated by clear identification of the specific target cell and intracellular target of benzene and its metabolites (Andrews and Snyder 1986). 

Crump KS. 1996. Risk of benzene-induced leukemia predicted from the pliofilm cohort. 

The potential for a nonhnear extrapolation from human data should also be considered. Some risk assessors have argued that benzene-induced leukemia and lymphoma is a threshold phenomenon, based on mechanistic considerations, and that the human data demonstrate such a threshold (Cox and Ricci 1992 Cox 1996 Yokley et al. 2006). However, regulatory risk assessors have not yet accepted these arguments for benzene (Bailer and Hoel 1989 ERA 1998 OEHHA 2001). Considerations include the multiple genotoxic metabolites of benzene, a nonlinear production of protein and DNA adducts in humans (saturated at higher benzene doses), and the difficulty of establishing dose-response relationships at lower doses with the available animal and human data (Bailer and Hoel 1989 Henderson et al. 1992 Turteltaub and Mani 2003 Rappaport et al. 2005 Lin et al. 2007). 

NADPH quinone oxido-reductase 1 Pro187Ser variant occurring with about 5% frequency is functionally almost completely deficient. Impaired activity associated with benzene toxicity and cancer chemotherapy induced leukemia. 

Numerous case reports and epidemiological studies suggest a leukemogenic action of benzene in humans—the leukemia tending to be acute and myeloblastic in type, often following aplastic changes in the bone marrow. Acute myelocytic leukemia may be preceded by myelodysplastic syndrome, a preleukemic state characterized by abnormal marrow architecture, inadequate hematopoiesis, and many cells with chromosome damage." Benzene may also induce chronic types of leukemia. ... 

Benzene can induce leukemia. The leukemogenic potential of benzene for humans has been estimated from data from three separate occupational epidemiological studies and their analyses (Bond et al. 1986b Infante 1977 Ott et al. 1978 Paxton et al. 1994a, 1994b Rinsky et al. 1981, 1987 Wong et al. 1983). Additional studies of workers in China may be found in the literature (Li et al. 1994 Travis et al. 1994 ... 

Benzene is a very widely used solvent and industrial chemical and a component of petroleum. It is a ubiquitous air pollutant and is formed as a decomposition product in fruit and soft drinks that are preserved with benzoates. Benzene is a known leukemogen and the one to which other leukemia-causing chemicals are compared. I37-39 Even low level exposure to benzene has been shown to induce leukemia. I39 40 Benzene has also been associated with lung and nasopharynx cancers. ... 

Inhibition of topoisomerase It (topoll) by benzene and its metabolites represents a potential mechanism by which benzene eould induce its chromosome-altering and leukemogenic effects. Figure 19.5.1 ineludes proposed mechanism. The inhibition of enzymatic activity at the closed elamp and other stages of the catalytic cycle in bone marrow cells would likely result in DNA breakage, the formation of chromosomal aberrations, and could potentially result in leukemia-associated chromosomal translocations. ... 

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