The process of leukemogenesis.

Irons, Richard D.; Stillman, Wayne S.

doi:10.1289/ehp.961041239

Cited by 38 publications

(15 citation statements)

References 95 publications

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“…Occupational exposure to benzene is widely thought to cause leukemias that are similar to t-AML and t-MDS. 18–20 In this study, the benzene metabolite, HQ, induced cytogenetic changes characteristic of both melphalan and etoposide. HQ at levels between 5 and 20 μM dose-dependently induced del(7q) and t(21;?…”

Section: Discussionmentioning

confidence: 60%

A comparison of the cytogenetic alterations and global DNA hypomethylation induced by the benzene metabolite, hydroquinone, with those induced by melphalan and etoposide

Z¹,

Zhang²,

Peng³

et al. 2010

Leukemia

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Specific cytogenetic alterations and changes in DNA methylation are involved in leukemogenesis. Benzene, an established human leukemogen, is known to induce cytogenetic changes through its active metabolites including hydroquinone (HQ), but the specific alterations have not been fully characterized. Global DNA hypomethylation was reported in a population exposed to benzene, but has not been confirmed in vitro. In this study, we examined cytogenetic changes in chromosomes 5, 7, 8, 11 and 21, and global DNA methylation in human TK6 lymphoblastoid cells treated with HQ for 48 h, and compared the HQ-induced alterations with those induced by two well-known leukemogens, melphalan, an alkylating agent, and etoposide, a DNA topoisomerase II inhibitor. We found that rather than inducing cytogenetic alterations distinct from those induced by melphalan and etoposide, HQ induced alterations characteristic of each agent. HQ induced global DNA hypomethylation at a level intermediate to melphalan (no effect) and etoposide (potent effect). These results suggest that HQ may act similar to an alkylating agent and also similar to a DNA topoisomerase II inhibitor in living cells, both of which may be potential mechanisms of benzene toxicity. In addition to cytogenetic changes, global DNA hypomethylation may be another mechanism underlying the leukemogenicity of benzene.

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Section: Discussionmentioning

confidence: 60%

A comparison of the cytogenetic alterations and global DNA hypomethylation induced by the benzene metabolite, hydroquinone, with those induced by melphalan and etoposide

Z¹,

Zhang²,

Peng³

et al. 2010

Leukemia

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“…CLL appears to be similar to other hematologic malignancies whose pathogenesis involves structural changes on the chromosomal level that cause mutational changes on the molecular level, altering important cellular functions, and, ultimately, leading to malignant transformation of a cell (Irons and Stillman 1996). Therefore, at the level of DNA damage, there is no basis for the assumption that the association between ionizing radiation exposure and CLL risk would be zero.…”

Section: Discussionmentioning

confidence: 99%

Ionizing Radiation and Chronic Lymphocytic Leukemia

Richardson

Wing

Schroeder

et al. 2005

Environ Health Perspect

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The U.S. government recently implemented rules for awarding compensation to individuals with cancer who were exposed to ionizing radiation while working in the nuclear weapons complex. Under these rules, chronic lymphocytic leukemia (CLL) is considered to be a nonradiogenic form of cancer. In other words, workers who develop CLL automatically have their compensation claim rejected because the compensation rules hold that the risk of radiation-induced CLL is zero. In this article we review molecular, clinical, and epidemiologic evidence regarding the radiogenicity of CLL. We note that current understanding of radiation-induced tumorigenesis and the etiology of lymphatic neoplasia provides a strong mechanistic basis for expecting that ionizing radiation exposure increases CLL risk. The clinical characteristics of CLL, including prolonged latency and morbidity periods and a low case fatality rate, make it relatively difficult to evaluate associations between ionizing radiation and CLL risk via epidemiologic methods. The epidemiologic evidence of association between external exposure to ionizing radiation and CLL is weak. However, epidemiologic findings are consistent with a hypothesis of elevated CLL mortality risk after a latency and morbidity period that spans several decades. Our findings in this review suggest that there is not a persuasive basis for the conclusion that CLL is a nonradiogenic form of cancer.

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“…Occupational exposure to benzene is widely thought to cause leukemias that are similar to t-AML and t-MDS (44, 56, 128). AML and MDS both arise from genetically altered CD34+ stem or progenitor cells in the bone marrow (70) and are characterized by many different types of recurrent chromosome aberrations (71, 76).…”

Section: Mechanisms Of Benzene Carcinogenicity: Mechanisms Of Myeloidmentioning

confidence: 99%

Advances in Understanding Benzene Health Effects and Susceptibility

Smith

2010

Annu. Rev. Public Health

326

247

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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.

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The process of leukemogenesis.

Cited by 38 publications

References 95 publications

A comparison of the cytogenetic alterations and global DNA hypomethylation induced by the benzene metabolite, hydroquinone, with those induced by melphalan and etoposide

A comparison of the cytogenetic alterations and global DNA hypomethylation induced by the benzene metabolite, hydroquinone, with those induced by melphalan and etoposide

Ionizing Radiation and Chronic Lymphocytic Leukemia

Advances in Understanding Benzene Health Effects and Susceptibility

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