Inhibition of azoxymethane-induced rat colon carcinogenesis by potassium hydrogen D-glucarate

While calcium D-glucarate was shown to inhibit chemical carcinogenesis in v arious animal models, the effect of potassium hydrogen D-glucarate has not been extensively investigated. In the present study, potassium hydrogen D-g lucarate markedly inhibited azoxymethane (AOM)-induced colon carcinogenesis in male F344 rats. Potassium hydrogen D-glucarate (PHG) or potassium hydro gen carbonate (PHC) were administered to rats in a diet (140 mmol/kg). Cont inual post-initiation treatment with potassium hydrogen D-glucarate reduced both tumor incidence and multiplicity at sacrifice by ca. 60%, while PHC h ad no effect. Amelioration of overexpression of the beta G gene in rat colo n carcinomas was observed using RT-PCR and Northern blot analysis. We hypot hesize that previously demonstrated conversion of PHG to D-glucaro-1,4-lact one, a potent inhibitor of beta-glucuronidase (beta G), may be responsible for this effect. The mechanism of PHG inhibition of colon carcinogenesis ma y also involve suppression of cell proliferation and possibly alterations i n cholesterol synthesis or cholesterol metabolism to bile acids. In conclus ion, PHG possesses excellent potential as a natural, apparently nontoxic in hibitor to prevent colon cancer.