TY - JOUR

T1 - Effects of dietary antioxidants and 2-amino-3-methylimidazo[4,5-f]- quinoline (IQ) on preneoplastic lesions and on oxidative damage, hormonal status, and detoxification capacity in the rat

AU - Breinholt, Vibeke Miller

AU - Mølck, Anne-Marie

AU - Svendsen, Gitte Winkel

AU - Daneshvar, Bahram

AU - Vinggaard, Anne Marie

AU - Poulsen, Morten

AU - Dragsted, Lars Ove

N1 - (Ekstern)

PY - 2003

Y1 - 2003

N2 - 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.

AB - 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.

KW - GST-P foci

KW - Induction of DNA damage by dietary antioxidants

KW - Lycopene

KW - Quercetin

KW - Resveratrol

UR - http://www.scopus.com/inward/record.url?scp=0141543856&partnerID=8YFLogxK

U2 - 10.1016/S0278-6915(03)00122-4

DO - 10.1016/S0278-6915(03)00122-4

M3 - Journal article

C2 - 12909264

AN - SCOPUS:0141543856

VL - 41

SP - 1315

EP - 1323

JO - Food and Chemical Toxicology

JF - Food and Chemical Toxicology

SN - 0278-6915

IS - 10

ER -