Inhibition of benzo[a]pyrene-DNA adduct formation by Aloe barbadensis Miller

Abstract

The antigenotoxic and chemopreventive effect of Aloe barbadensis Miller (polysaccharide fraction) on benzo[a]pyrene (B[a]P)-DNA adducts was investigated in vitro and in vivo. Aloe showed a time-course and dose-dependent inhibition of [3H]B[a]P-DNA adduct formation in primary rat hepatocytes (1 x 106 cells/ml treated with [3H]B[a]P (4 nmol/ml). At concentrations of 0.4-250 μg/ml aloe, the binding of [3H]B[a]P metabolites to rat hepatocyte DNA was inhibited by 9.1-47.9%. Also, in rat hepatocytes cultured for 3-48 h with aloe (250 μg/ml) and [3H]B[a]P (4 nmol/ml), [3H]B[a]P-DNA adducts were significantly reduced by 36% compared with [3H]B[a]P alone. Aloe also inhibited cellular uptake of [3H]B[a]P in a dose-dependent manner at a concentration of 0.4-250 μg/ml by 6.3-34.1%. After a single oral administration of B[a]P to male ICR mice (10 mg/mouse), benzo[a]pyrene diol epoxide I (BPDE-I)-DNA adduct formation and persistence for 16 days following daily treatment with aloe (50 mg/mouse) were quantitated by enzyme-linked immunosorbent assay using monoclonal antibody 8E11. In this animal model, BPDE-I-DNA adduct formation was significantly inhibited in various organs (liver, kidney, forestomach and lung) (P < 0.001). When mice were pretreated with aloe for 16 days before B[a]P treatment, inhibition of BPDE-I-DNA adduct formation and persistence was enhanced. Glutathione S-transferase activity was slightly increased in the liver but cytochrome P450 content was not affected by aloe. These results suggest that the inhibitory effect of aloe on BPDE-I-DNA adduct formation might have a chemopreventive effect by inhibition of B[a]P absorption.