Introduction
Excessive exposure to benzene has been recognized for over a century as causing damage to the bone marrow, resulting in reduced numbers of blood cells and eventually aplastic anemia. More recently, it has been acknowledged that another consequence of benzene exposure is the development of various types of leukemia. Although there is agreement among many researchers that the toxic byproducts of benzene metabolism can cause direct harm to the bone marrow, the specific mechanisms underlying the development of leukemia remain unclear and require further investigation.
This issue is of broader interest because it has been observed that individuals treated with alkylating agents for tumor remission may subsequently develop leukemia similar to that induced by benzene exposure, highlighting the concept of "second cancer." Additionally, there is a growing body of literature focused on understanding the intricate structure of the bone marrow, including the identification of specialized environments called "niches" where various types of stem cells and other cells reside. Some of these niches may contain cells capable of initiating leukemia.The regulation of stem cell behavior, including differentiation and proliferation, through both inter- and intra-cellular communication will ultimately determine the fate of these transformed stem cells.
Investigating how these cells evade regulatory mechanisms that normally prevent them from contributing to leukemia is another crucial area of research. While previous studies on benzene-induced bone marrow damage have primarily focused on identifying which benzene metabolites are responsible for leukemogenesis, the current focus should shift towards understanding how these metabolites specifically alter the biology of bone marrow cells. This article explains the link between leukemia and benzene.
What Is Benzene?
Benzene (C6H6, CAS 71-43-2) is the most basic aromatic hydrocarbon. It is a transparent, colorless liquid with a distinct gasoline-like smell, is highly flammable, and evaporates readily. Presently, benzene is a significant product in the global petrochemical industry. Historically, it served various purposes, such as an ingredient in printing inks, a solvent for organic substances, and a fundamental component in the chemical and pharmaceutical sectors.
Benzene, a chemical utilized commercially since the late 1800s, was among the earliest industrial substances shown to impact workers' health on a large scale. Workers were exposed to varying levels of benzene, from low concentrations believed to not affect humans to high concentrations reaching hundreds of parts per million (ppm). High levels of exposure resulted in workers experiencing decreased numbers of red blood cells, white blood cells, and/or platelets in their bloodstream. A reduction in all three cell types, termed pancytopenia, typically indicated the onset of aplastic anemia, confirming the bone marrow as the primary target organ for benzene toxicity. It is now understood that exposure to benzene can also lead to the development of myelodysplasia, a condition preceding leukemia, as well as various forms of blood cancer known as leukemias.
Benzene is a highly combustible and extremely volatile liquid compound in the aromatic hydrocarbon family. It has found extensive application in numerous industrial operations as a solvent or primary material. Particularly at the onset of the twentieth century, benzene was widely utilized in various workplace settings, notably in the printing, shoe manufacturing, and rubber industries. While the initial recognition of benzene's link to aplastic anemia dates back earlier, investigations into its association with leukemia began in the 1930s. In a landmark move, Italy became one of the pioneering nations in 1963 to enact legislation banning benzene as a solvent in occupational activities.
What Is the Relationship Between Benzene and Leukemia?
Establishing the link between benzene exposure and leukemia proved more challenging than demonstrating its role in causing aplastic anemia. While decreases in blood cell counts due to benzene exposure could be observed within a few months, there was often a lag of several years before leukemia developed.
The following are the points that prove the link between benzene and leukemia:
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Early reports linking benzene exposure to leukemia were primarily based on individual cases. Notably, in 1938, Penati and Vigliani from the Institute for Industrial Medicine at the University of Turin provided initial estimates of leukemia frequency among workers exposed to benzene between 1928 and 1938, reporting 60 cases of aplastic anemia and 10 cases of leukemia.
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Following World War II, Vigliani and colleagues from the University of Milan conducted surveys among benzene-exposed workers from 1942 to 1975, reporting cases of hemopathy leading to death, including aplastic anemia and leukemia.
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A similar study conducted in Pavia identified numerous cases of hemopathy, with deaths attributed to aplastic anemia and leukemia.
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Additionally, in Istanbul, Turkey, from 1955 to 1960, a significant increase in hemopathies, including leukemia, was observed among shoemakers after switching to benzene-containing solvents.
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In the mid-1970s, the United States Occupational Health and Safety Administration (OSHA) aimed to establish a new permissible occupational exposure limit for benzene. While Vigliani and Aksoy's work provided strong evidence, OSHA initiated a new study of benzene-exposed workers in the rubber industry, culminating in one report of a notable increase in myeloid leukemias among benzene-exposed workers in Akron, Ohio.
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Subsequent investigations, notably by Yin, Li, and their Chinese and United States colleagues at the National Cancer Institute, attracted significant attention. Their studies, including a cohort comparison of control subjects and benzene-exposed workers, revealed significant increases in various blood-related cancers and supported the concept of benzene as a leukemogen.
All these studies prove that benzene is linked to aplastic leukemia, directly or indirectly.
Conclusion
The goal of this discussion has been to revisit certain aspects of the relationship between benzene and the individuals it could affect. However, the review is limited due to time and space constraints, preventing a more comprehensive presentation of the benzene literature. Due to these investigations and the subsequent implementation of regulations prohibiting benzene, workplace exposure conditions have shifted over recent decades.
The resultant decrease in concentrations has spurred researchers to explore fresh biomarkers for exposure and delve into associated health issues. However, some areas require more research, such as examining the benzene metabolites that impact the metabolism of benzene in the human body, factors affecting healthy cells and leukemia cells, and the role of hepatotoxic agents in the body.
