Fruits and vegetables protect against the genotoxicity of heterocyclic aromatic amines activated by human xenobiotic-metabolizing enzymes expressed in immortal mammalian cells.
Heterocyclic aromatic amines (HAAs) can be formed during the cooking of meat and fish at elevated temperatures and are associated with an increased risk for cancer. On the other hand, epidemiological findings suggest that foods rich in fruits and vegetables can protect against cancer. In the present study three teas, two wines, and the juices of 15 fruits and 11 vegetables were investigated for their protective effect against the genotoxic effects of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). To closely mimic the enzymatic activation of these HAAs in humans, genetically engineered V79 Chinese hamster fibroblasts were employed that express human cytochrome P450-dependent monooxygenase (hCYP) 1A2 (responsible for the first step of enzymatic activation) and human N(O)-acetyltransferase (hNAT) 2*4 or human sulfotransferase (hSULT)1A1*1 (responsible for the second step of enzymatic activation): V79-hCYP1A2-hNAT2*4 for IQ activation and V79-hCYP1A2-hSULT1A1*1 for PhIP activation. HAA genotoxicity was determined by use of the comet assay. Black, green and rooibos tea moderately reduced the genotoxicity of IQ (IC(50)=0.8-0.9%), whereas red and white wine were less active. From the fruit juices, sweet cherry juice exhibited the highest inhibitory effect on IQ genotoxicity (IC(50)=0.17%), followed by juices from kiwi fruit, plum and blueberry (IC(50)=0.48-0.71%). The juices from watermelon, blackberry, strawberry, black currant, and Red delicious apple showed moderate suppression, whereas sour cherry, grapefruit, red currant, and pineapple juices were only weakly active. Granny Smith apple juice and orange juice proved inactive. Of the vegetable juices, strong inhibition of IQ genotoxicity was only seen with spinach and onion juices (IC(50)=0.42-0.54%). Broccoli, cauliflower, beetroot, sweet pepper, tomato, chard, and red-cabbage juices suppressed IQ genotoxicity only moderately, whereas cucumber juice was ineffective. In most cases, fruits and vegetables inhibited PhIP genotoxicity less strongly than IQ genotoxicity. As one possible mechanism of antigenotoxicity, the inhibition of activating enzymes was studied either indirectly with diagnostic substrates or directly by measuring CYP1A2 inhibition. Only sour cherry, blueberry, and black currant juices suppressed the first step of HAA enzymatic activation, whereas most plant-derived beverages inhibited the second step.
Platt
K L
KL
Institute of Toxicology, University Medical Center, Johannes Gutenberg-University Mainz, Obere Zahlbacher Str. 67, 55131 Mainz, Germany. platt@uni-mainz.de
Edenharder
R
R
Aderhold
S
S
Muckel
E
E
Glatt
H
H
D000588:Amines / Q000633:toxicity*; D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D001628:Beverages; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D004789:Enzyme Activation; D005638:Fruit; D006571:Heterocyclic Compounds / Q000633:toxicity*; D009153:Mutagens / Q000633:toxicity*; D014675:Vegetables
D000588:Amines; D016587:Antimutagenic Agents; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D006571:Heterocyclic Compounds; D009153:Mutagens