The potential beneficial or adverse affect of prolonged dietary administration of moderate to high doses (1-100 mg/kg diet) of the
antioxidants,
lycopene,
quercetin and
resveratrol or a mixture of
lycopene and
quercetin was investigated in male F344 rats. Selected markers for toxicity and defense mechanisms were assayed in blood, liver and colon and the impact of the
antioxidant administrations on putative preneoplastic changes in liver and colon was assessed. The dietary
carcinogen, 2-amino-3-methylimidazo[4,5-f]
quinoline (IQ) (200 mg/kg diet) served as a
pro-oxidant, genotoxicity and general toxicity control. IQ increased the levels of
protein and
DNA oxidation products in plasma, the area of
glutathione S-transferase-placental form positive (GST-P) foci in the liver as well as the number of colonic
aberrant crypt foci (ACF). All
antioxidants and the
antioxidant combination significantly increased the level of lymphocytic DNA damage, to an extent comparable with the effect induced by IQ. In contrast to the control group where no GST-P foci were detected, GST-P foci were detected in animals exposed to
quercetin,
lycopene and the combination of the two. However, the increase in the volume of GST-P foci did not reach statistical significance. The present results indicate that moderate to high doses of common dietary
antioxidants can damage lymphocyte
DNA and induce low levels of preneoplastic liver lesions in experimental animals. Long-term exposure to moderate to high doses of
antioxidants may thus via pro-oxidative mechanisms and non-oxidative mechanisms modulate
carcinogenesis.