Numerous studies have reported associations between benzene exposure and the induction of lymphomas in mice. Studies by Cronkite et al. (21) and Snyder et al. (22) in the early 1980s showed inhalation of benzene caused excess lymphomas in various mouse strains. The 1986 National Toxicology Program carcinogenicity bioassay of benzene also reported an excess of malignant lymphomas, as well as other cancers, in male and female B6C3F1 mice. Studies in Italy by Maltoni et al. (23) showed excesses of lymphosarcomas in RF/J mice. As with many rodent toxicology studies, there has been debate over the relevance of these findings to humans.
There are many similarities between leukemia induced by benzene and that induced by chemotherapy with alkylating agents, so-called therapy-related leukemia, and the latter has been proposed as a model of chemical-induced leukemogenesis (24). Treatment of primary cancers with alkylating agents such as melphalan dramatically increases risks of secondary leukemias. Interestingly, as discussed by Krishnan and Morgan in this issue, numerous studies show that alkylating agent chemotherapy also increases the risk of secondary NHL as well as leukemia. Thus, benzene may act like alkylating agents and ionizing radiation in inducing both leukemias and lymphomas.