Isoprene is produced in combustion processes and is widely used as an industrial chemical. It is a natural product emitted by plants and endogenously produced by humans and other mammals. Therefore, exposure to
isoprene from both endogenous and exogenous sources is unavoidable and occurs during the entire human life. Based on evaluations of the International Agency for Research on
Cancer (IARC),
isoprene has been classified in Group 2B (possibly carcinogenic to humans). In the present work, we have demonstrated, by use of the single-cell gel electrophoresis assay (SCGE or comet assay), that
isoprene is able to induce DNA damage in peripheral blood mononuclear cells (PBMCs) in the presence of metabolic activation. In addition, treatment of cells with the main
isoprene mono-
epoxide (
EPOX I) induced time- and dose- dependent DNA damage in both PBMCs and human leukaemia cells (HL60). The metabolic activation system, represented by rat liver post-mitochondrial fractions (S9), was obtained from rats that had been treated - or not - with inducing agents such as
phenobarbital and
ethanol. The inclusion of S9 fractions (4mg
protein/mL) from non-induced or
phenobarbital-induced rats resulted in a statistically significant enhancement of
isoprene genotoxicity. A different pattern was obtained by the addition of
ethanol-induced S9, which appeared highly genotoxic by itself even in the absence of
isoprene. Reducing the concentration of
ethanol-induced S9 to 0.25mg
protein/mL resulted in a considerable enhancement of
isoprene genotoxicity. In the absence of clear epidemiological evidence of the carcinogenicity of
isoprene in humans, the results of this study seem to be particularly important since they add new findings to support the classification of this chemical as possibly carcinogenic to humans.