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1.
Pfau Wolfgang; Brockstedt Ulrike; Sohren Klaus-Dieter; Marquardt Hans 《Carcinogenesis》1994,15(5):877-882
Food-derived aminoimidazoazarenes have been shown to be mutagenicand carcinogenic and to form covalent DNA adducts. 32P-Post-labellinganalysis of DNA modified with these heterocyclic amines (HA),including 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ), 2-amino-1-methyl-6-phenylimid-azo[4,5-b]pyridine(PhIP), 2-amino-3,4-dimethylimidazo [4,5-fquinoline (MeIQ),2-amino-3,4,8-trimethylimidazo [4,5-f1 quinoxaline (4,8-DiMeIQx),2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline (7,8-DiMeIQx)and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) hasresulted in considerable interlaboratory variation in the characteristicpatterns of DNA adduct spots, with up to six being detectedfor each compound. Similar complex patterns were observed whenazido-derivatives of HA were photoreacted with calf thymus DNA.When deoxyguanosine 3'-monophosphate was modified with the azidoderivatives and analysed using the 32P-post-labelling procedure,one major spot was observed for IQ, 4,8-DilMeIQx, 7,8-DiMeIQxor PhIP and two major spots for MeIQ or MeIQx. In each case,these adducts were chromatographically indistinguishable fromthe major adducts formed with DNA. No major adduct spots wereobserved when 3'-phosphate derivatives of deoxyadenosine, deoxycytidineor thymidine were reacted with the azido-derivatives of HA.In an attempt to identify the additional spots, azido derivativesof PhIP or IQ were reacted with the synthetic homopolymer poly(dG)·poly(dC),the alternating copolymer poly(dC-dG) or a synthetic oligonucleotide(TTT-GTTTTTTCTTTCCCT): in each case a reduced number of adductspots were detected. The introduction of an additional nucleaseP1 hydrolysis step following the labelling reaction furtherreduced the number of adduct spots to only one or two majorspots. Reversed-phase HPLC analysis showed that the number ofpeaks of radioactivity was also reduced to one or two, presumablycorresponding to the [32P]-5'-monophosphate deoxyguanosine adducts.We suggest that many of the additional spots commonly observedin conventional 32P-post-labelling analysis of HA-modified DNAare adducted oligonucleotides that are partly resistant to hydrolysisby micrococcal nuclease and spleen phosphodiesterase but aresusceptible to hydrolysis by nuclease P1. 相似文献
2.
Monoclonal mouse IgG1 and IgG3 antibodies were developed tothe food mutagens, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine(PhIP) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline(4,8-DiMeIQx) in order to make specific and sensitive detectionand purification systems suitable for biological samples. Theantibodies were developed with the strategy that cross-reactionwith analogues modified in the N2-position was desirable. Competitiveenzyme-linked immunosorbent assays (ELISA) with 50% inhibitionby 0.46 pmol food mutagen were developed. The epitopesrecognized by the antibodies have been characterized by ELISAusing 52 synthetic analogues and metabolites of PhIP, 4,8-DiMeIQx,and other food mutagens. One of the anti-PhIP antibodies onlyrecognizes PhIP and those PhIP-analogues which have minor modificationsin the N2-amino group, whereas the other, 7B7-1, is less stringentand also recognizes several other modified metabolites, includingbulky adducts at the N2-amino group e.g. the major guanine anddeoxyguanosine adducts isolated from PhIP-modified DNA. Theantibodies to DiMeIQx also recognize the food mutagens 2-amino-3,4-dimethylimidazo[4,5-f]quinoxaline(4-MeIQx), 2-amino-3, 8-dimethylimidazo[4, 5-f]quinoxaline (8-MeIQx),and the corresponding quinolines (4-MeIQ and 8-MeIQ). Two ofthese antibodies only bind analogues with minor modificationsin the free amino group, whereas analogues with major modificationsin this position, including a deoxyguanosine adduct, react withthe third antibody. Urine samples and faecal extracts from 3H-PhIPor 2-14C-DiMeIQx dosed rats were analysed by these ELISA assays,and high correlations between radioactivity and response inthe ELISA assays were observed. Urine samples and faecal extractsfrom 3H-PhIP-dosed rats were purified on an affinity columncontaining the less stringent anti-PhIP antibody, 7B7-1. Theaffinity column was found by high performance liquid chromatography(HPLC) analysis to concentrate exclusively labelled material.This affinity column also bound PhIP-related materials fromdilute samples of acid hydrolysed PhIP-DNA with high efficiency.Only 相似文献
3.
Simple methods for quantifying mutagenic heterocyclic aromatic amines in food products 总被引:3,自引:0,他引:3
Two solid-phase extraction methods were developed for the determinationof mutagenic heterocyclic aromatic amines in heated meat products.The copper phthalocyanine (CPC) tandem extraction was performedon coupled cartridges of diatomaceous earth and CPC-derivatizedSephasorb HP, followed by further clean-up on Sephasorb HP.Parts per billion levels of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline(MeIQx) and its homologs as well as 2-amino-3-methylimidazo[4,5-f]quinoline(IQ), 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoline (MeIQ), 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine(PhIP), amino--carboline (AC), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole(Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2),harman (H) and norharman (NH) can then be simultaneously quantifiedby HPLC with UV detection. The propylsulfonyl silica gel (PRS)tandem extraction is a one-step clean-up method on coupled cartridgesof diatomaceous earth and PRS, suitable for the determinationof MeIQx, IQ and their homologs, as well as the glutamic acidpyrolysates 2-amlno-6-methyldipyrido[1,2-a:3',2']imidazole (Glu-P-1)and 2-aminodipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2). 4,7,8-TriMeIQxor 7,8-DiMeIQx were used as internal standards. Four grams ofsample or less are required for analysis. The recovery of theamineswas between 46 and 83% and the detection limit was in the lowp.p.b. range with coefficients of variation ranging between5 and 18%. The major mutagenic contaminant found in meat extractswas MeIQx (from <1 to 44 p.p.b.), followed by 4,8-DiMeIQx(1.35 p.p.b.) whereas the major contaminant in friedmeat was PhIP (2348 p.p.b.), followed by MeIQx (5.18.3p.p.b.), AC (3.28.9 p.p.b.) and 4,8-DiMeIQx (1.32p.p.b.).The co-mutagens NH and H were found in fried meat atlevels of 8.719 p.p.b. and 34.8 p.p.b. respectively. 相似文献
4.
2-Amino-3, 8-dimethylimidazo[4, 5-f]quinoxaline (MelQx) wastransformed to at least 10 metabolites in suspensions of hepatocytesisolated from Aroclor 1254 treated rats. Combining biochemicaldata such as effects on MeIQx metabolism of metabolic modulatorsand incorporation of radioisotopic sulfur with UV, mass and1H-NMR spectroscopy, we elucidated the structures of six metabolites.About 40% of the MeIQx was transformed to 2-amino-3, 8-dimethylimidazo[4,5-f]quinoxalin-4(or5)-yl sulfate. Other oxygenated metaboliteswere 2-amino-8-hydroxymethy13-methylimidazo[4, 5-f)quinoxalin-4(or5)-yl sulfate and 2-amino-4(or5)-ß-D-glucuronopyranosyloxy-3,8-dimethylimidazo[4, 5-f]quinoxaline. Evidence was obtainedthat a glutathione conjugate was formed. This metabolite, andthe other oxygenated metabolites were probably formed in P-450catalyzed reactions. Two metabolites, 2-ß-D-glucurono-pyranosylamino-3,8-dimethylimidazo[4, 5-f)quinoxaline and the N(3, 8-dimethylimidazo[4,5-f]quinoxaline-2-yl)sulfamate, were direct conjugates of MeIQx. 相似文献
5.
An efficient and convenient method for the purification of mutagenic heterocyclic amines in heated meat products 总被引:2,自引:0,他引:2
A simple and efficient method for the purification of mutagenicheterocyclic amines from heated meat products has been developed.In only two steps, namely extraction of raw material on Kieselgurfollowed by medium pressure liquid chromatography on SephasorbHP, very clean fractions with high recovery rates of mutageniccompounds were obtained, thus allowing isolation and quantitationby high performance liquid chromatography (HPLC) with UV detection.The method was validated on both food grade and bacterial beefextracts as well as fried beef. In 15 gsamples of beefextracts, levels up to 70 p.p.b. (ng/g) of 2-amino-3-methyl-imidazo[4,5-f]quinoline(IQ), 890 p.p.b. of 2-amino-3, 8-di-methylimidazo[4,5-f]quinoxaline (MeIQx) and up to 8 p.p.b. of 2-amino-3, 4,8-trimethylimidazo[4, 5-f]quinoxaline (4, 8-DiMeIQx) were determined.In fried beef, 1p.p.b. of 2-amino-1-methyl-6phenylimidazo[4,5-b]pyridine(PhIP) and 1 p.p.b. of MeIQx were measured. Thequantitative results of beef samples were in agreement withresults from determinations using immunoaffinity chromatography/HPLCor liquid chromatography coupled with mass spectrometry. MeIQxcould be quantified in fried beef down to 1ng/g of fresh beefmaterial. According to assays performed with reference standardsof tryptophan and glutamic acid pyrolysis products, the methodcould also be extented to quantitate other heterocyclic amines. 相似文献
6.
Occurrence of mutagenic/carcinogenic heterocyclic amines in meat and fish products, including pan residues, prepared under domestic conditions 总被引:5,自引:0,他引:5
Some typical Swedish meat and fish products, e.g. bacon, beefburgers,meatballs, Baltic herring, salmon, smoked fish, black puddingand sausages, and their corresponding pan residues, were analysedby HPLC for their content of mutagenic/carcinogenic heterocyclicamines (HAs). The products were cooked using recommended domesticcooking conditions concerning temperature, time and frying equipmentThe amount of HAs was low in most products, though the amountwas higher in the pan residues, especially in the pan residuefrom the frying of Falun sausage, which contained 18.5 ng HAs/gcooked product Mostly MelQx (2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline)and 4,8-DiMeIQx (2-amino-3,4,8-trimethylimidazo[4,5-f]-quinoxaline)were found, being 0.032.8 ng MelQx/g and n.d.-3.4 ng4,8-DiMeIQx/g cooked product in the food products and 0.0573ng MelQx/g and n.d.-2.8 ng 4,8-DiMelQx/g cooked product in thepan residues. High levels of IQ (2-amino-3-methylimidazo[4,5-f]quinoline),10.5 ng/g, were only found in well-done bacon and a correlationwas seen between fat content and IQ formation. Low levels ofMelQ (2-amino-3,4-dimethylimidazo[4,5-f]quinoline) and PhIP(2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine) were foundin the foods. 相似文献
7.
Major routes of metabolism of the food-borne carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in the rat 总被引:1,自引:0,他引:1
Turesky R.J.; Aeschbacher H.U.; Wurzner H.P.; Skipper P.L.; Tannenbaum S.R. 《Carcinogenesis》1988,9(6):1043-1048
The metabolic fate of 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline(MeIQx), a carcinogen formed in cooked meat and fish, has beeninvestigated in male Sprague-Dawley rats. Five metabolites wererecovered from bile of animals given an intragastric dose of{2-14C]MeIQx. These accounted for nearly all of the radioactivityin bile. The chemical structures of these metabolites were elucidatedby proton NMR, UV and mass spectroscopy. Three structures maybe assigned unambiguously: two sulfamates, N-(3,8.dimethylimidazo[4,5f]quinoxalin-2-yl)sulfamic acid and N-(8-hydroxymethyl-3-methylimidazo[4,5f]quinoxalin-2-yl)sulfamic acid, and N-(8-one glucuronide, N2(ß-1-glucosiduronyl)-2-amino-3,8-dimelhyliinidazo[4,5f]quinoxaline In addition, an acetyl and a glucosiduronylconjugate of 5-hydroxy-MeIQx were observed. The spectral evidencedid not allow an unambiguous assignment of the site of conjugation.The two glucuronides were excreted in urine and the sulfamateof MeIQx was found in feces as well as urine. All five metaboliteswere found to be non-mutagenic to Salmonella typhimurium TA98with or without metabolic activation. The glucuronide conjugateswere found also to be non-mutagenic when ß- glucuronidasewas incorporated with S-9 mixture in the mutation assay, andthus all appear to be detoxification products. The previouslyreported metabolite, 2-amino-8-hydroxymethyl-3-methylimidazo[4,5f]quinoxalinewhich is mutagenic to Salmonella typhimurium TA98 with metabolicactivation, was identified as a minor component in both urineand feces. 相似文献
8.
Turesky R.J.; Aeschbacher H.U.; W?rzner H.P.; Skipper P.L.; Tannenbaum S.R. 《Carcinogenesis》1989,10(9):1765
A metabolite of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline(MeIQx) was incorrectly characterized in this paper. The metabolitewas thought to be an acetyl conjugate of the 5-hydroxyl-atedderivative of MeIQx. This assignment is incorrect. The correctassignment is a sulfate conjugate of 5-hydroxy-MeIQx, 2-amino-3,8-dimethylirnidazo[4,5-f]quinoxaUn-5-yl-sulfate.This conclusion is based upon repurified sample analyzed by1H NMR and 13C NMR, enzyme hydrolysis assays, IR spectro-scopyand FAB/MS (accurate mass measurement). 相似文献
9.
Knize Mark G.; ?vervik Eva; Midtvedt Tore; Turteltaub Kenneth W.; Happe James A.; Gustafsson Jan-?ke; Felton James S. 《Carcinogenesis》1989,10(8):1479-1484
The aromatic amine mutagen, [l4C]2-amino-3,4-8-trimethyl-imidazo[4,5-f]quinoxaline(4,8-DiMeIQx), which is derived from cooked food, was administeredto conventional and germ-free AGUS rats previously fed eithera semi-synthetic diet containing the cytochrome P-450 inducerß-naphtho-flavone (BNF) or a control diet withoutBNF. The germ-free animals had longer fecal transit times andlower induction of 7-ethoxyresorufin-O-deethylase activity thanconventional rats. Induction with BNF caused a greater percentageof the radioactivity to be excreted in the feces of both germ-freeand conventional rats. Feeding BNF also caused a 4-fold inductionin germ-free and a 24-fold induction in conventional rat intestinalenzyme levels. Analysis of the urinary and fecal metabolitesshowed no consistent differences between conventional and germ-freerats in the metabolite profile. Major metabolites were identifiedas 8-hydroxymethyl-DiMeIQx, N-acetyl-8-hydroxymethyl-DiMelQx,and 3-N-dimethyl-4-hydroxy-methyl-DiMelQx. The data from thisstudy indicate that intestinal microflora do not play a majorrole in the metabolism of 4,8-DiMeIQx, but the induction ofintestinal enzymes does affect the route and rate of excretion. 相似文献
10.
Carmichael Paul L.; Stone Elaine M.; Grover Phillip L.; Gusterson Barry A.; Phillips David H. 《Carcinogenesis》1996,17(8):1769-1772
Cultures of human mammary epithelial cells were treated withone of seven heterocyclic amine food mutagens [2-amino-3-methylimidazo[4,5-f)quinoline (IQ), 2-amino-3, 4-dimethylimidazo[4, 5-f)quinoline(MelQ), 2-amino-3, 8-di-methylimidazo[4, 5-f]quinoxaline (MeIQx),2-amino-3, 4, 8-trimethylimidazo[4, 5-f]quinoxaline (4, 8-DiMelQx)2-amino-3, 7, 8-trimethylimidazo[4, 5-f]quinoline (7, 8-DiMelQx),2-amino-3, 4, 7, 8-tetramethylimidazo[4, 5-f]quinoxaline (4,7, 8-TriMelQx) or 2-amino-1-methy16-phenylimidazo[4,5-b] pyridine (PhlP)], four nitropyrenes (1-nitropyrene (1-NP),1, 3-dinitropyrene (1, 3-DNP), 1, 6-dinitropyrene (1, 6-DNP)or 1, 8-dinitropyrene (1, 8-DNP) or the Polycyclic aromatichydrocarbon dibenzo[a, l]pyrene (DB[a, l]P). DNA isolated fromthe cultures was analysed by 32P-post-labelling and in eachcase the presence of carcinogen-DNA adducts was detected. Thepatterns and numbers of adducts obtained when human mammarycell DNA digests were separated on polyethyleneimine-celluloseTLC were found to closely resemble those previously demonstratedto be present in the DNA of tissues from rodents and other primatestreated with the same agents. Up to six DNA adducts were detectedin human breast cells treated with IQ and MelQ. Fewer adducts(13) were detected following treatment with MelQx orits methylated derivatives, whilst PhIP gave rise to at leastfour distinct adduct spots. Five adduct spots were detectedin breast cells treated with DB[a, l]P or with 1-NP, but feweradduct spots were formed by 1, 3-, 1, 6- and 1, 8-DNP. Thesedata demonstrate the ability of human breast epithelial cellsto activate to DNA binding species a range of carcinogenic compoundsknown to be present in the human diet or to which humans areknown to be exposed environmentally. 相似文献
11.
Johansson Maria A.E.; Fay Laurent B.; Gross Glan A.; Olsson Kjell; Jagerstad Margaretha 《Carcinogenesis》1995,16(10):2553-2560
Mixtures of creatinine, glucose and various single amino acidswere heated at 180°C for 10 min in an aqueous model system.The heated mixtures all showed mutagenic activity, ranging from80 to 2400 TA98 revertant colonies/µmol creatinine withmetabolic activation. Testing of HPLC fractions for mutagenicactivity showed each mixture to contain several mutagenic components,some of which corresponded to known heterocyclic amines andothers to unknown compounds. The presence of 2-amino-3-methyl-imidazo[4,5-f]quinoxaline,2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline and 2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxalinein most of the samples was established using HPLC with photodiodearray detection and liquid chromatography/mass spectrometrywith electrospray interface and single ion monitoring. In addition,2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine,3-amino-1,4-di-methyl-5H-pyrido[4,3-b]indole and 3-amino-1-methyl-5H-pyrido[4,3-b]indoleand the co-mutagenic compounds 9H-pyrido[3,4-bindole and 1-methyl-9H-pyrido[3,4-b]indolewere detected in some samples. 相似文献
12.
Kim In-Soo; Wakabayashi Keiji; Kurosaka Reiko; Yamaizumi Ziro; Jinno Fumihiro; Koyota Souichi; Tada Akihiro; Nukaya Haruo; Takahashi Makoto; Sugimura Takashi; Nagao Minako 《Carcinogenesis》1994,15(1):21-26
By monitoring the mutagenicity to a new Salmonella tester strain,YG1024, which has a much higher level of 0- acetyltransferaseactivity than S.typhimurium TA98, we found two new mutageniccompounds in bacteriological-grade beef extract. One of them(compound I), which had a similar UV spectrum to that of 2-amlno-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx), was isolated and shown toaccount for {small tilde}2% of the total mutagenicity of thematerials adsorbed to blue cotton, and its concentration wasestimated to be 6.0 ng/g beef extract. This amount of compoundin beef extract was insufficient to allow measurements of variousspectra, but its level was increased {small tilde}9-fold byheating beef extract with creatine and threonine at 200°Cfor 5 h. From UV and mass spectra of the compound obtained frombeef extract heated with creatine plus threonine, it was deducedto be a hydroxymethyl derivative of anminodimethylimidazoquinoxaline.Compound I was isolated from the urine of rats given 4,8-DiMeIQxand identified as 2-amino-4-hydroxymethyl-3,8-dimethylimidazo[4,5-f]quinoxaline (4-CH2OH-8-MeIQx) by 1H-NMR analysis. 4-CH2OH-8-MeIQxinduced 326 000 revertants of YG1024 and 99 000 revertants ofTA98 per µg in the presence of S9 mix. 相似文献
13.
A gas chromatographicmass spectrometric assay has beendeveloped for the simultaneous measurement of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline(MeIQx) and 2-amino-3,4,8-dimethylimidazo[4,5-f]quinoxaline(DiMeIQx) in fried beef. The method employs capillary columngas chromatography, electron capture negative ion chemical ionisationmass spectrometry and a stable isotope labelled analogue ofMeIQx (the synthesis of which is described) as common internalstandard. Two patties of lean minced beef which had been cookedseparately were analysed and found to contain both compounds(patty 12.4 ng MeIQx/g meat, 1.2 ng DiMeIQx/g meat; patty21.3 ng MeIQx/g meat, 0.5 ng DiMeIQx/g meat). Neithercompound was present in the meat prior to cooking. 相似文献
14.
Heterocyclic aromatic amine formation in grilled bacon, beef and fish and in grill scrapings 总被引:3,自引:0,他引:3
Gross Gian A.; Turesky Robert J.; Fay Laurent B.; Stillwell W.G.; Skipper Paul L.; Tannenbaum Steven R. 《Carcinogenesis》1993,14(11):2313-2318
The heterocyclic aromatic amines (HAAs) 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3, 8-di-methylimidazo[4,5-f)quinoxaline(MelQx), 2-amino-3, 4, 8-tri-methylimidazo[4, 5-f)quinoxaline(4, 8-DiMeIQx) and 2-amino 相似文献
15.
Ochiai Masako; Nagaoka Hiroaki; Wakabayashi Keiji; Tanaka Yoshino; Kim Seon-Bong; Tada Akihiro; Nukaya Haruo; Sugimura Takashi; Nagao Minako 《Carcinogenesis》1993,14(10):2165-2170
The carcinogenic heterocyclic amine 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline(MeIQx) is widely distributed in cooked foods. The nucleaseP1 method increased the sensitivity of the standard 32P-postlabelinganalysis about 1000-fold for detection of MeIQx-DNA adducts.The recovery of MeIQx-DNA adducts by the nuclease P1 methodwas determined to be about 50% using liver DNA of a rat treatedwith [14C]MeIQx intragastrically. By the nuclease P1 methodfive adducts were detected in the liver DNA of rats fed MeIQxand two of them, including the most abundant one, were identifiedas MeIQx-deoxyguanosine adducts by comparison with the adductsformed in in vitro reactions of N-acetoxy-2-amino-3,8-dimethylimidazo[4,5-f)quinoxalinewith the four 2'-deoxyribonucleotides. The most abundant adductin vivo was identified as N2-(deoxyguanosin-8-yl)-MeIQx 3',5'-diphosphate(3',5'-pdGp-C8-MeIQx). MeIQx-DNA adduct levels in human tissuescould be determined by the nuclease P1 modification of the 32P-postlabelingmethod in combination with HPLC, and thus provide informationon the roles of MeIQx in human carcinogenesis. 相似文献
16.
Synergistic enhancement of hepatic foci development by combined treatment of rats with 10 heterocyclic amines at low doses 总被引:3,自引:1,他引:3
Hasegawa Ryohei; Miyata Emiko; Futakuchi Mitsuru; Hagiwara Akihiro; Nagao Minako; Sugimura Takashi; Ito Nobuyuki 《Carcinogenesis》1994,15(5):1037-1041
Potential synergism between 10 carcinogenic heterocyclic amines[3-amino-l,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole(Trp-P-2), 2-amino-6 methyldipyrido[l,2-a:3',2'-d]imidazole(Glu-P-1), 2-ammo-dipyrido[l,2-a:3',2'-d]imidazoIe (Glu-P-2),2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethyl-imidazo[4,5-f]quinoline(MeIQ), 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx),2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA 相似文献
17.
Frandsen Henrik; Grivas Spiros; Turesky Robert J.; Andersson Rolf; Dragsted Lars O.; Larsen John C. 《Carcinogenesis》1994,15(11):2553-2558
The covalent binding of the mutagenic N2-hydroxy metaboilteof the food mutagen 2-amino-3,4,8-trimethyl-3H-lmldazo[4,5-f]quinoxaline(4,8-DiMeIQx) to 2'-deoxy-nudeosides and DNA was investigatedin vitro and in vivo. N2-Hydroxy-4,8-DiMeIQx reacted to a smallextent spontaneously with 2-deoxyguanosine. However, acetylatlonof N2-hydroxy-4,8-DiMeIqx with acetic anhydride to form theN2-acetoxy derivative prior to reaction with 2-deoxyguanosineresulted in much higher yield of adduct. N2-Acetoxy-4,8-DiMeIQxdid not form adducts with 2'-deoxy- adenosine, 2'-deoxycytldlneor 2'-deoxythymldlne. The adduct formed between the N metaboliteof 4,8- DiMeIQx and 2-deoxyguanosine was analysed by mass spectrometryand NMR spectroscopy and the structure of the adduct was shownto be N2-Acetoxy-4,8-DiMeIQx. N2-Acetoxy-4,8-DiMeIQx. reactedwith calf thymus DNA and formed a covalently bound 4,8-DiMeIQxresidue, which could not be removed by repeated precipita tionsor solvent extractions. The 4,8-DiMeIQx-DNA was hydrolysed enzymaticallywith nuclease P1/acid phosphat ase and HPLC analysis showedthat 70% of the bound mutagen was recovered as N2-Acetoxy-4,8-DiMeIQx.An additional minor adduct accounting for 相似文献
18.
Effect of cooking temperature on the formation of heterocyclic amines in fried meat products and pan residues 总被引:4,自引:0,他引:4
Skog Kerstin; Steineck Gunnar; Augustsson Katarina; Jagerstad Margaretha 《Carcinogenesis》1995,16(4):861-867
Frequent consumers of meat have an increased risk of colorectalcancer and possibly also of breast, stomach, pancreas and urinarybladder cancer. Bacon, Falusausage, ground beef,meatballs, pork belly, pork chops and sliced beef account formore than one-third of the intake of fried meat of the populationof Stockholm of age 5075. These dishes were fried atfour temperatures (150, 175, 200 and 225 °C) representingnormal household cooking practices in Stockholm. Heterocyclicamines in these dishes were analysed using solid-phase extractionand HPLC. The heterocyclic amines 2-amino-3-methylimidazo[4,5-f]quinoline(IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx),2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP) wererecovered. The formation of IQ was favoured by moderate cookingtemperatures; IQ was detected in one meat sample cooked at 150°Cand in some pan residues. The yield of MeIQx, DiMeIQx and PhIPincreased with the temperature. For several of the meat dishes,the content of heterocyclic amines in the pan residue was aslarge or larger than for corresponding piece of meat. The highestlevels of MeIQx were 23.7 ng/g in the meat and 233 ng/g in thepan residue. Corresponding data for DiMeIQx were 2.7 and 4.1ng/g and for PhIP 12.7 and 82.4 ng/g. The study leaves littledoubt that mutagenic heterocyclic amines are ingested by thepopulation of Stockholm, and added to previous epidemiologicalstudies from the same area, the combined data are consistentwith human carcinogenicity of heterocyclic amines. However,analytical epidemiological studies are needed before any statementon causality can be made. 相似文献
19.
Snyderwine Elizabeth G.; Davis Cindy D.; Nouso Kazuhiro; Roller Peter P.; Schut Herman A.J. 《Carcinogenesis》1993,14(7):1389-1395
The 32P-postlabeling method was used to examine the adductsin DNA, polynucleotides, and mononucleotides reacted in vitrowith the N-hydroxy and N-acetoxy derivatives of 2-amino-3-methylimidazo[4,5-f]quinoline(IQ), 2-amino-3, 8-dimethylimidazo[4,5-f]quinoxaline (MelQx)or 2-amino-1-methy1-6-phenylimidazo[4,5-b]pyridine (PhIP). Adductprofiles were compared to those found in vivo in liver of cynomolgusmonkeys fed IQ, MeIQx or PhIP. The N-acetoxy derivatives ofIQ, MelQx and PhIP (generated in situ from the correspondingN-hydroxylamine in the presence of acetic anhydride) each formedthree principal adducts in DNA. Adduct 1 of IQ, MeIQx and PhlPwas chromatographically identical to the 32P-labeled bis(phosphate)derivative of N-(deoxyguanosin-8-yI)-IQ, N-(deoxyguanosin-8-yI)-MeIQx,and N-(deoxyguanosin-8-yl)-PhIP respectively, and this adductcomprised 相似文献
20.
Davis Cindy D.; Schut Herman A.J.; Adamson Richard H.; Thorgeirsson Unnur P.; Thorgeirsson Snorri S.; Snyderwine Elizabeth G. 《Carcinogenesis》1993,14(1):61-65
Cooked meat, poultry and fish contain a number of mutagenicand carcinogenic heterocyclic amines, including 2-amino-3-methylimidazo[4,5-f]quinoline(IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).In the present study we examined the capacity of hepatic microsomesfrom Fischer 344 rats, cynomolgus monkeys and humans to metabolicallyactivate IQ, MeIQx and PhIP in vitro using the Ames Salmonellamutagenicity assay. The mutagenic activation of IQ was similaramong the three species; however, there were significant differencesamong the species in the activation of PhIP and MeIQx. Livermicrosomes from humans showed the greatest capacity to activatePhIP and MeIQx, followed by rats, and then monkeys. The largestdifferences between the species were observed when MeIQx wasused as the mutagen. MeIQxDNA adducts formed in vivowere then compared among rats and monkeys given MeIQx by gavage(20 mg/kg/day, 10 doses). 32P-Postlabeling analysis, carriedout under intensification conditions, was used to examine MeIQxDNAadducts in the liver, kidney, heart, colon and white blood cells.MeIQxDNA adducts were highest in all tissues examinedfrom male rats, followed by female rats, and much lower in monkeys.In the liver, the total MeIQxDNA adduct levels of monkeyswere {small tilde}19 and {small tilde}10 times lower than inmale and female rats respectively. In extrahepatic tissues,the differences in MeIQxDNA adduct levels between monkeysand rats were even greater. The results suggest that the lowlevel of MeIQxDNA adducts found in vivo in cynomolgusmonkeys reflects a low capacity to activate MeIQx via the hepaticcytochrome P450 monooxygenase system. 相似文献