The Mechanism of Benzene-induced Leukemia
by Mika Pringle Tolson
Benzene, a commonly used chemical, is known to cause leukemia in humans. What is not known, however, is its detailed mechanism of action. Christopher Frantz, a doctoral student in Environmental Toxicology at UC Riverside and recipient of a TSR&TP graduate student fellowship for this year, is trying to identify if, and how, benzene and benzene metabolites act on the nuclear protein (enzyme), topoisomerase II, resulting in chromosomal damage and eventually leukemia. Topoisomerase II interacts with DNA during replication and transcription, and Frantz is pursuing the idea that "A metabolite of benzene enters the bone marrow and affects this protein (topoisomerase II). This mechanism is thought to be responsible for some of the leukemias that are induced by benzene." According to Frantz, "Benzene is a ubiquitous chemical in the environment, so everyone is exposed to it. We pretty much know if you're exposed to enough of it, your bone marrow will be affected and this can eventually lead to leukemia. There are arguments as to the length of exposure time and exposure concentrations that will result in leukemias but it's well documented as an effect." Occupational exposures account for the greatest amount of high level exposures, but benzene is also found in cigarette smoke and automobile exhaust. Benzene exposure is even greater in developing countries where laws governing the use of chemicals and enforcement is less than optimal. For example, there have been reports of a relatively high incidence of leukemia in areas in China where benzene-containing solvents are used in manufacturing operations without proper safety precautions. Benzene has not only been linked to leukemia, but as Frantz says, "there's a subset of diseases that benzene can cause, such as aplastic anemia or myelodysplastic syndrome, things that are similar to leukemia in a broad sense that they are the result of benzene's toxic effects on the bone marrow." With his background in animal science and toxicology, Frantz is investigating the mechanisms of benzene-induced carcinogenesis because he's interested in applying his knowledge to help understand the effects that toxics can have on human health. He hopes the results of his research will provide us with tools for better risk assessment and help to change policies on acceptable exposures. "If it's shown that lower levels of exposure can cause these effects it will provide more evidence to support a reduction in the permissable exposure levels allowed in industry," explains Frantz. After he completes his Ph.D. research, Chris Frantz would like to continue working in toxicology. He says, "I enjoy the challenges of toxicology research and hopefully I can continue to apply my education toward solving toxicological problems."
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