title: Lycopene modulates initiation of N-nitrosodiethylamine induced hepatocarcinogenesis: studies on chromosomal abnormalities, membrane fluidity and antioxidant defense system.
abstract: Oxidative damage due to free radicals generated during nitrosamine metabolism has been suggested as one of the major cause for the initiation of hepatocarcinogenesis. Lycopene, is a well known antioxidant and have promising preventive potentials, however the mechanism of action remain hypothetical and unclear. To investigate the involvement of lycopene extracted from tomatoes (LycT) against oxidative stress induced deleterious effect of N-nitrosodiethylamine (NDEA) on cellular macromolecules, female Balb/c mice were divided in four groups: Control, NDEA (cumulative dose of 200mg NDEA/kg body weight injected intraperitoneally in 8 weeks), LycT (5mg/kg body weight given orally on alternate days, throughout the study) and LycT+NDEA (co-administration of LycT and NDEA). NDEA treatment commenced after 2 weeks of LycT administration. At the end of NDEA exposure i.e., at 10th week, enhanced activities of hepatic phase I enzymes, levels of reactive oxygen species (ROS), lipid peroxidation (LPO) was observed in NDEA group which may have contributed in chromosomal aberrations, enhanced micronucleated cell score, membrane fluidity and serum liver marker enzymes. A significant decrease in enzymatic and non-enzymatic antioxidant system could delineate the mechanism behind such NDEA insults. LycT pre-treatment to NDEA challenged group showed lower chromosomal abnormalities, micronucleated cells score, ROS, LPO levels and liver enzymes. Lycopene aids in normalizing the membrane fluidity and enhancing the activity of antioxidant enzymes and reduced glutathione which could account for the reduced oxidative damage in LycT+NDEA group. It seemed that lycopene supplementation target multiple dys-regulated pathways during initiation of carcinogenesis. Thus, dietary supplementation with lycopene can serve as an alternate measure to intervene the initiation of carcinogenesis.
authors.affiliation: Department of Biophysics, Basic Medical Sciences Block, Panjab University, Chandigarh 160014, India.
authors.forename: Prachi
authors.initials: P
authors.lastname: Gupta
authors.forename: Mohinder Pal
authors.initials: MP
authors.lastname: Bansal
authors.forename: Ashwani
authors.initials: A
authors.lastname: Koul
mesh_terms: D000818:Animals; D002338:Carotenoids / Q000737:chemistry / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002869:Chromosome Aberrations / Q000187:drug effects; D004052:Diethylnitrosamine / Q000633:toxicity; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D000077276:Lycopene; D018551:Solanum lycopersicum / Q000737:chemistry; D008560:Membrane Fluidity / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D002338:Carotenoids; D004052:Diethylnitrosamine; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D000077276:Lycopene
keywords: Chromosomal-abnormalities; Hepatocarcinogenesis; Lycopene; Membrane-fluidity; Micronucleus; Oxidative-stress