Modulation of xenobiotic-metabolizing enzymes and redox status during chemoprevention of hamster buccal carcinogenesis by bovine lactoferrin

Abstract

Objective Chemoprevention by dietary constituents has emerged as a novel approach to control oral cancer incidence. We therefore evaluated the chemopreventive efficacy of bovine milk lactoferrin (bLF) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. Methods Hamsters were divided into four groups. The right buccal pouches of animals in groups 1 and 2 were painted with 0.5% DMBA three times a week for 14 wk. Animals in group 2, received in addition, basal diet containing 0.2% bLF. Group 3 animals were given 0.2% bLF alone. Group 4 animals served as control. The status of carcinogen-metabolizing enzymes, the extent of lipid peroxidation and glutathione-dependent antioxidants in the buccal pouch and liver as well as bone marrow micronuclei incidence were used as biomarkers. Results All the hamsters painted with DMBA alone for 14 wk, developed HBP carcinomas that showed diminished lipid peroxidation and increased activities of carcinogen-metabolizing enzymes and antioxidants with enhanced bone marrow micronuclei. In the liver of tumor bearing animals, the increase in phase I enzymes and lipid peroxidation was accompanied by reduced activities of antioxidant and phase II detoxification enzymes. Administration of bLF decreased the incidence of DMBA-induced micronuclei and HBP carcinomas by decreasing phase I enzymes, modulating lipid peroxidation and enhancing antioxidant and phase II enzyme activities. Conclusion The chemopreventive effects of bLF is mediated by reducing DMBA-induced genotoxicity and modulating carcinogen-metabolizing enzymes and oxidant-antioxidant profile in the target organ as well as in the liver.