Antimutagenic effects of lycopene and tomato purée.

Several health benefits, including protection from tumors at various anatomic sites, such as the lungs, stomach, and prostate gland, have been attributed to tomatoes and tomato-based products. Among tomato carotenoids, lycopene is the most active antioxidant, although it has many other biological effects, but data on its antimutagenic effects are scarce and often discrepant. The aim of our work was to determine the protective effects of lycopene, with regard to mutagenicity, via two indirect mutagens/carcinogens-2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and aflatoxin B1 (AFB1) and the direct mutagen/carcinogen N-nitroso-N-methylurea (MNU)--using the Ames and micronucleus tests. The significant, dose-dependent, antimutagenic effects of two concentrations of lycopene (30 µg and 300 µg per plate) were demonstrated at various concentrations of both AFB1 and IQ in two strains of Salmonella typhimurium (TA98 and TA100). The protective effects of lycopene relative to MNU were lower in comparison to its protective effects relative to AFB1 and IQ. Mice treated for 3 days with different doses of lycopene (either 25 or 50 mg/kg of body weight) prior to administration of individual mutagens resulted in a significant reduction of micronuclei numbers in the micronucleus test. Tomato purée (tested using the Ames test and AFB(1)) revealed a much stronger, dose-dependent, antimutagenic effect compared with corresponding doses of pure lycopene. Results indicate that lycopene has antimutagenic effects, although the effects are lower than that of tomato purée, which contains a complex mixture of bioactive phytochemicals. The antimutagenic effect is connected with the chemoprotective role of lycopene, tomatoes, and tomato products in the prevention of carcinogenesis.

Chromosomal damage in peripheral blood lymphocytes of newly diagnosed cancer patients and healthy controls.

BACKGROUND: The majority of human cancers arise from cells unable to maintain genomic stability. Recent prospective studies indicated that enhanced chromosomal aberrations (CAs) frequencies are predictive of gastrointestinal and lung cancers. However, studies on incident cancer patients are lacking; thus, we investigated chromosomal damage in newly diagnosed cancer patients and healthy individuals. METHODS: We analyzed chromosomal damage in peripheral blood lymphocytes in a group of 300 incident cancer patients (with different malignancies) in comparison with 300 healthy controls. RESULTS AND CONCLUSIONS: The frequencies of aberrant cells (ACs) and CAs were significantly higher in patients (2.38 +/- 1.56 and 2.53 +/- 1.69, respectively) as compared with controls (1.81 +/- 1.31 and 1.94 +/- 1.47, respectively, P < 0.01). The percentual difference in chromatid-type aberrations (CTAs) between patients and controls was moderately significant (1.37 +/- 1.20 and 1.11 +/- 0.99, respectively, P

Renal effects of HMG-CoA reductase inhibition in a rat model of chronic inhibition of nitric oxide synthesis.

BACKGROUND/AIMS: In addition to their lipid-lowering effects, HMG-CoA reductase inhibitors (statins) induce a variety of pleiotropic actions that have been recently studied in the area of cardiovascular and renal protection. In the present studies we sought to determine whether statins retain beneficial effects in the experimental model of NO deficiency achieved by chronic administration of a pressor dose of L-arginine analogue N-nitro-L-arginine-methyl ester (L-NAME). METHODS: To address this issue, blood pressure (BP), renal function (GFR), and albuminuria were determined in rats treated for 4 weeks with L-NAME, L-NAME + atorvastatin (ATO), and in untreated controls. In addition, renal cortical protein expression of caveolin 1 (CAV1), vascular endothelial growth factor (VEGF), and activity of RhoA were also determined. RESULTS: L-NAME administration resulted in sustained elevation of BP, decreased GFR, and in higher albuminuria as compared to control animals. Co-administration of ATO with L-NAME normalized albuminuria and prevented decreases in GFR in L-NAME rats without having an impact on pressor effects of L-NAME. CAV1 protein expression was similar in all groups of rats. In contrast, VEGF expression and RhoA activity was increased in L-NAME-treated animals, and normalized with co-administration of ATO. CONCLUSION: Treatment with ATO exerts early nephroprotective effects in the NO-deficient model of hypertension. These effects could be mediated by amelioration of VEGF expression and reduction of RhoA activity.