Benzene as a cause of lymphoproliferative disorders.
There is a long standing issue concerning the strength of evidence relating benzene to lymphocytic neoplasms. Because benzene is a known cause of human acute myelogenous leukemia there has been little reason for organizations such as the International Agency for Research on Cancer (IARC) or the US National Toxicology Program (NTP) to perform standard hazard identification reviews of benzene as a possible cause of other cancers such as lymphomas. Increased understanding of underlying mechanisms of carcinogenesis, as is reflected in the greater scope given to mechanistic evidence in assigning overall sufficiency of evidence for carcinogenicity by both IARC and NTP, suggests that the evidence supporting benzene as a cause of lymphoma likely has passed the threshold required for being listed as a known causal relationship. A broad range of genotoxic effects in the lymphocytes of benzene-exposed workers has been well documented, as has the role of chromosomal effects in carcinogenesis. There is also increasing evidence of a close relationship between lymphoid tumors and the types of myeloid tumors known to be caused by benzene. This includes the not infrequent finding of biphenotypic lineage as well as the formation of lymphoid as well as myeloid leukemias following chemotherapy. Studies of the mechanism of benzene toxicity are consistent with a relatively non-specific mechanism capable of producing multiple chromosomal changes, and there is evidence that the early hematopoietic stem cell, which is believed to be targeted by benzene in causing myeloid cancers, is also the progenitor of lymphocytic cell types. Furthermore, the classification of lymphomas has evolved so that non-Hodgkin lymphoma now includes such formerly distinct disorders as chronic lymphocytic leukemia and multiple myeloma, and there is less of a distinction between leukemia and non-leukemia forms of lymphoma.
Goldstein
Bernard D
BD
Graduate School of Public Health, University of Pittsburgh, 130 Desoto Street, Crabtree A710, Pittsburgh, PA 15261, USA. bdgold@pitt.edu
D000818:Animals; D001554:Benzene / Q000009:adverse effects*; D004249:DNA Damage; D006801:Humans; D008223:Lymphoma / Q000139:chemically induced / Q000145:classification / Q000453:epidemiology; D008232:Lymphoproliferative Disorders / Q000139:chemically induced* / Q000453:epidemiology; D051379:Mice
D001554:Benzene