A review of the role of benzene metabolites and mechanisms in malignant transformation: Summative evidence for a lack of research in nonmyelogenous cancer types

The aromatic hydrocarbon benzene is a well-recognised haematotoxin and carcinogen associated with malignancy in occupational environments. Primary benzene metabolites phenol, catechol, and hydroquinone are implicated in the progression from cytotoxicity to carcinogenicity, and malignant transformation in myelogenous cell lineage is hypothesised to encompass a complex multistep process involving gene mutations in cell signalling and mitosis, oncogene activation, downregulated immune-mediated tumour surveillance, anti-apoptotic activities, and genetic susceptibility. Several mechanisms of carcinogenicity are proposed but none are accepted widely as causative. Involvement of covariables such as duration and frequency of benzene exposure, metabolite concentration, and degree of biological interactions provides a theoretical framework for a multiple mechanistic model to explain cytotoxic-malignant transformation. Despite significant research in myeloid leukaemias, limited biological and epidemiological studies on benzene and its metabolites in nonhaematopoietic malignancies suggests more research is needed to determine its role in contributing to other cancer types.