Cyclohexanol is a basic industrial chemical widely used because of its versatility as an industrial
solvent. No studies have been conducted to evaluate the carcinogenic/co-carcinogenic hazards associated with
cyclohexanol exposure. In male Fisher 344 rats liver preneoplastic lesions were induced by
N-nitrosodiethylamine (150 mg/Kg) i.p., followed by the
tumor promoter 2-acetylaminofluorene (2-AAF: 20 mg/kg) orally administered on three consecutive days before partial
hepatectomy. The
cyclohexanol administration in this hepatocarcinogenesis assay revealed that it has a strong
tumor co-promoter potential. There is clear evidence that oxidative stress and the
CYP2E1 are components of
carcinogenesis. Although no changes in the lipid peroxidation levels were observed between treated and untreated animals, a significant increase in
CYP2E1 expression was observed when
cyclohexanol was administered 24 h after the last
2-AAF dose. On the other hand, levels of the proliferation markers
PCNA and Ki-67 were not increased
after treatment with
cyclohexanol, but a marked downregulation of the Bax proapoptotic
protein was found exclusively in mitochondrial extracts of animals treated with
cyclohexanol. This study represents the first report of the ability of
cyclohexanol-induced lesions, when administered simultaneously with
2-AAF, to potentiate the development of preneoplastic liver.