Co‐carcinogenic effect of cyclohexanol on the development of preneoplastic lesions in a rat hepatocarcinogenesis model

Abstract

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.

Resveratrol Downregulates Cyp2e1 and Attenuates Chemically Induced Hepatocarcinogenesis in SD Rats

“…Recent studies have also shown the critical role of Cyp2e1 overexpression in the progression of hepatocarcinogenesis 12 , 23 , 24 . Furthermore, in some previous studies, Cyp2e1 was induced in the liver in DEN→2-AAF groups 25 , 26 , suggesting overexpressed Cyp2e1 has a potential role in DEN+2-AAF-induced hepatocarcinogenesis. Here, we found that treatment with REV or DADS (an inhibitor of Cyp2e1) two weeks after DEN-initiation efficiently decreased the level of Cyp2e1 protein and reduced the number and area of GST-P foci (Figs.…”

“…Multiple studies have shown the important role of CYP2E1 overexpression in generating oxidative stress 12 , 31 , 32 . Cyp2e1 induction was also found in DEN+2-AAF-induced hepatocarcinogenesis 25 , 26 , indicating the potential role of Cyp2e1 in this process. Here, we found that treatment of REV or DADS two weeks after DEN-initiation efficiently decreased the level of Cyp2e1 protein and reduced the number and area of GST-P foci (Figs.…”

Volatile organic compounds in head and neck squamous cell carcinoma—An in vitro pilot study

“…Huang and colleagues found significantly higher concentrations of cyclohexanol in the headspace of pleural effusions in lung cancer vs. benign tumors (Huang et al, ). In addition, cyclohexanol had a co‐carcinogenic effect in the development of rat liver tumors (Marquez‐Rosado et al, ). Whether cyclohexanol is now the cause or the effect of malignancies is currently completely unclear.…”

Cyclohexanol [MAK Value Documentation in German language, 2010]

“…Eine Kanzerogenitätsstudie mit Cyclohexanol wurde bisher nicht durchgeführt. Cyclohexanol allein zeigte weder eine initiierende noch eine promovierende Wirkung, war jedoch in einer artifiziellen Untersuchung bei hohen Dosierungen leicht kopromovierend(Márquez-Rosado et al 2007). Cyclohexanon, das über Cyclohexanol metabolisiert wird, wurde aufgrund von Schilddrüsentumoren bei der männlichen Ratte, die nicht mechanistisch erklärt werden konnten, in Kanzerogenitäts-Kategorie 3 B eingestuft (siehe Begründung "Cyclohexanon" 1994).…”