title: Anti-mutagenic and anti-carcinogenic potential of the carotenoid meso-zeaxanthin.
abstract: Meso-zeaxanthin was investigated for antimutagenic and anticarcinogenic activity, using the Ames test (Salmonella typhimurium strains TA 98, TA 100, TA 102 and TA 1535) with direct acting mutagens like sodium azide (NaN3) (5 μg/ plate), nitro-o-phenylendiamin (NPD) (20 μg/ plate), N-methyl- N'-nitro-N-nitrosoguanidine (MNNG) (1μg/ plate) and tobacco extract 50 mg/ plate) and with a mutagen needing microsomal activation, acetamidofluorene (AAF) ( 20 μg/ plate). The carotenoid was found to inhibit the mutagenicity induced by NaN3, NPD and MNNG in a concentration dependent manner, as well as that with AAF and the tobacco extract. Concentrations needed for 50 % inhibiton was found to be 50 μg/ plate for the chemical mutagens and 100 μg/ plate for tobacco extract. Using specific resorufin derivatives as substrates in vitro, the concentration of meso-zeaxanthin needed for 50 % inhibition of CYP1A2 (7-methoxyresorufin-O-demethylase) was 5 µg/ml, for CYP2B 1/2 (7- pentoxyresorufin-O-depentylase) was 8 µg/ml and for CYP1A1 (7-ethoxyresorufin-O-deethylase) was 12 µg/ml, while that of CYP 2E1 (aniline hydroxylase) was 7µg/ml and for CYP 1A, 2A, 2B, 2D and 3A (aminopyrene-N-demethylase) was 10.5 µg/ml. Evaluated using nitroso diethyl amine (NDEA) induced hepatocellular carcinoma in rats, treatment with meso-zeaxanthin reduced the tumor incidence when compared to the control group. The activity of glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and alkaline phosphatase was drastically elevated in both serum and liver tissue of NDEA alone treated control animals and meso-Zeaxanthin pretreated animals showed significant decrease to normal levels, in line with histopathological findings.
authors.affiliation: Amala Cancer Research Centre, Amala Nagar P.O, Kerala, India.
authors.forename: Alikunjhi P
authors.initials: AP
authors.lastname: Firdous
authors.forename: Edakkadath R
authors.initials: ER
authors.lastname: Sindhu
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Ramnath
authors.forename: Ramadasan
authors.initials: R
authors.lastname: Kuttan
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D016587:Antimutagenic Agents / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000517:prevention & control*; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012480:Salmonella Infections / Q000188:drug therapy / Q000382:microbiology; D012486:Salmonella typhimurium / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D024341:Xanthophylls / Q000494:pharmacology*; D065146:Zeaxanthins
chemical_list: D016588:Anticarcinogenic Agents; D016587:Antimutagenic Agents; D002273:Carcinogens; D009153:Mutagens; D024341:Xanthophylls; D065146:Zeaxanthins; C584722:meso-zeaxanthin; D019388:Cytochrome P-450 CYP1A2