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
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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. / Breinholt, Vibeke Miller; Mølck, Anne-Marie; Svendsen, Gitte Winkel; Daneshvar, Bahram; Vinggaard, Anne Marie; Poulsen, Morten; Dragsted, Lars Ove.
In: Food and Chemical Toxicology, Vol. 41, No. 10, 2003, p. 1315-1323.Research output: Contribution to journal › Journal article › Research › peer-review
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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 -
ID: 254727831