Benzo(a)pyrene (BaP) is a
polycyclic aromatic hydrocarbon widespread in the environment and closely associated to tobacco use, which is an important risk factor for highly incident
stomach cancer.
Menthol, a
monoterpene extracted from Mentha genus species, has multiple
biological properties, including anti-inflammatory and gastroprotective properties, but its effects on
carcinogenesis are still to be fully understood. Thus, we evaluated the modifying effects of Ment against BaP-induced forestomach
carcinogenesis. Female Swiss mice received BaP by intragastrical (i.g.) administration (50 mg/kg of
body weight [b wt], 2×/week), from weeks 1-5 weeks. Concomitantly, mice received
Menthol at 25 (Ment25) or 50 (Ment50) mg/kg b wt (i.g, 3×/week). Animals were euthanized at weeks 5 (n = 5 mice/group) or 30 (n = 10 mice/group). At week 5, both Ment doses reduced peripheral leukocyte blood genotoxicity 4 h after the last BaP administration, but only Ment50 attenuated this
biomarker 8 h after the last BaP administration. In accordance to these findings, both Ment interventions attenuated BaP-induced increase in the percentage of H2A.X-positive forestomach epithelial cells. Moreover, Ment50 reduced cell proliferation and apoptosis (i.e., Ki-67 and
caspase-3, respectively) in forestomach epithelium but exerted no significant effects on NFκB, and Nrf2
protein levels. At week 30, Ment50 reduced by ~55% the incidence of BaP-induced forestomach diffuse
hyperplasia and multiplicity of forestomach
tumors (
squamous cell papillomas and
carcinomas). Our findings indicate that Ment50, administered during initiation phase, attenuates forestomach
carcinogenesis by reducing early genotoxicity, cell proliferation, and apoptosis induced by BaP.