Effect of dietary constituents with chemopreventive potential on adduct formation of a low dose of the heterocyclic amines PhIP and IQ and phase II hepatic enzymes.
We conducted a study to evaluate dietary chemopreventive strategies to reduce genotoxic effects of the carcinogens 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). PhIP and IQ are heterocyclic amines (HCAs) that are found in cooked meat and may be risk factors for cancer. Typical chemoprevention studies have used carcinogen doses many thousand-fold higher than usual human daily intake. Therefore, we administered a low dose of [14C]PhIP and [3H]IQ and utilized accelerator mass spectrometry to quantify PhIP adducts in the liver, colon, prostate, and blood plasma and IQ adducts in the liver and blood plasma with high sensitivity. Diets supplemented with phenethylisothiocyanate (PEITC), genistein, chlorophyllin, or lycopene were evaluated for their ability to decrease adduct formation of [14C]PhIP and [3H]IQ in rats. We also examined the effect of treatments on the activity of the phase II detoxification enzymes glutathione S-transferase (GST), UDP-glucuronyltransferase (UGT), phenol sulfotransferase (SULT) and quinone reductase (QR). PEITC and chlorophyllin significantly decreased PhIP-DNA adduct levels in all tissues examined, which was reflected by similar changes in PhIP binding to albumin in the blood. In contrast, genistein and lycopene tended to increase PhIP adduct levels. The treatments did not significantly alter the level of IQ-DNA or -protein adducts in the liver. With the exception of lycopene, the treatments had some effect on the activity of one or more hepatic phase II detoxification enzymes. We conclude that PEITC and chlorophyllin are protective of PhIP-induced genotoxicity after a low exposure dose of carcinogen, possibly through modification of HCA metabolism.
Dingley
Karen H
KH
Biology and Biotechnology Research Program and Center for Accelerator Mass Spectrometry, Lawrence Livermore National Laboratory, Livermore, CA 94551, USA.
Ubick
Esther A
EA
Chiarappa-Zucca
Marina L
ML
Nowell
Susan
S
Abel
Steffen
S
Ebeler
Susan E
SE
Mitchell
Alyson E
AE
Burns
Stephanie A
SA
Steinberg
Francene M
FM
Clifford
Andrew J
AJ
D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage*; D015239:Arylsulfotransferase / Q000378:metabolism; D002250:Carbon Radioisotopes; D002338:Carotenoids / Q000008:administration & dosage; D002735:Chlorophyllides / Q000008:administration & dosage; D003106:Colon / Q000737:chemistry; D018736:DNA Adducts / Q000032:analysis / Q000378:metabolism*; D004032:Diet; D019587:Dietary Supplements; D019833:Genistein / Q000008:administration & dosage; D014453:Glucuronosyltransferase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007093:Imidazoles / Q000008:administration & dosage / Q000378:metabolism*; D017879:Isothiocyanates / Q000008:administration & dosage; D008099:Liver / Q000737:chemistry / Q000201:enzymology*; D000077276:Lycopene; D008297:Male; D009153:Mutagens / Q000008:administration & dosage / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D011467:Prostate / Q000737:chemistry; D011804:Quinolines / Q000008:administration & dosage / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D012709:Serum Albumin / Q000378:metabolism; D014316:Tritium
D016588:Anticarcinogenic Agents; D002250:Carbon Radioisotopes; D002735:Chlorophyllides; D018736:DNA Adducts; C096278:DNA-(2-amino-3-methylimidazo(4,5-f)quinoline) adduct; D007093:Imidazoles; D017879:Isothiocyanates; D009153:Mutagens; D011804:Quinolines; D012709:Serum Albumin; D014316:Tritium; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D002338:Carotenoids; C058305:phenethyl isothiocyanate; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D019833:Genistein; D016660:NAD(P)H Dehydrogenase (Quinone); D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D015239:Arylsulfotransferase; C007020:chlorophyllin; D000077276:Lycopene