Chromosome Damage from Biological Reactive Intermediates of Benzene and 1,3-Butadiene in Leukemia

The causes of leukemia remain largely unknown. Only ionizing radiation, benzene and various chemotherapy drugs are established causes in humans. While benzene is an established cause of acute myeloid leukemias, its ability to cause lymphocytic leukemias and the closely related lymphomas and multiple myeloma remains highly controversial (1-4). The concentration at which it significantly increases leukemia risk is also contentious. For example, it was recently claimed in a leading journal that benzene has a dose threshold of 200 p.p.m.-years for leukemia induction (4), although there is clearly information that benzene induces leukemia and other hematological changes at much lower doses than this (3,5) and that its effects are likely to be linear down to background levels (6). Other occupational and environmental chemicals are suspected leukemogens, but are not established as such and controversy surrounds their classification as human carcinogens. One such compound is 1,3-butadiene. This compound is widely used in the rubber industry and is a product of incomplete combustion. Its' potential classification as a human carcinogen on the basis of epidemiological studies (7,8) showing higher rates of leukemia in exposed workers is under consideration by numerous agencies (9). To throw further light on these important questions concerning the human risk posed by benzene and butadiene, we have examined the ability of benzene, butadiene and their reactive intermediates to produce the types of chromosome damage thought to be etiologically important in leukemia and lymphoma in exposed humans and in human cells in vitro. This paper summarizes our recent findings and discusses their impact on the risk assessments for benzene and butadiene.