Inhibition of benzo[a]pyrene-DNA adduct formation by Aloe barbadensis Miller.
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 (1x10(6) cells/ml) treated with [3H]B[a]P (4 nmol/ml). At concentrations of 0.4-250 microg/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 microg/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 microg/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.
Kim
H S
HS
Division of Toxicology, College of Pharmacy, Sung Kyun Kwan University, Suwon City, Kyunggi-Do, South Korea.
Lee
B M
BM
D000504:Aloe / Q000737:chemistry*; D000818:Animals; D001564:Benzo(a)pyrene / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002478:Cells, Cultured; D018890:Chemoprevention; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D018736:DNA Adducts / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D051381:Rats; D017207:Rats, Sprague-Dawley; D013347:Subcellular Fractions / Q000378:metabolism; D014316:Tritium
D018736:DNA Adducts; D010936:Plant Extracts; C056612:benzo(a)pyrene-DNA adduct; D014316:Tritium; D001564:Benzo(a)pyrene; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase