INHIBITION OF BENZO[A]PYRENE-DNA ADDUCT FORMATION BY ALOE-BARBADENSISMILLER

The antigenotoxic and chemopreventive effect of Aloe barbadensis Mille r (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 [H-3]B[a]P-DNA adduct formation in primary rat hepatocytes (1x10(6) cells/ml) treated with [H-3]B[a]P (4 nmol/ml). A t concentrations of 0.4-250 mu g/ml aloe, the binding of [H-3]B[a]P me tabolites to rat hepatocyte DNA was inhibited by 9.1-47.9%. Also, in r at hepatocytes cultured for 3-48 h with aloe (250 mu g/ml) and [H-3]B[ a]P (4 nmol/ml), [H-3]B[a]P-DNA adducts were significantly reduced by 36% compared with [H-3]B[a]P alone. Aloe also inhibited cellular uptak e of [H-3]B[a]P in a dose-dependent manner at a concentration of 0.4-2 50 mu g/ml by 6.3-34.1%. After a single oral administration of B[a]P t o male ICR mice (10 mg/mouse), benzo[a]pyrene diol epoxide I(BPDE-I)-D NA adduct formation and persistence for 16 days following daily treatm ent with aloe (50 mg/mouse) were quantitated by enzyme-linked immunoso rbent 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 pret reated with aloe for 16 days before B[a]P treatment, inhibition of BPD E-I-DNA adduct formation and persistence was enhanced, Glutathione S-t ransferase 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.