Use of antioxidants to minimize the human health risk associated to mutagenic/carcinogenic heterocyclic amines in food (original) (raw)
Related papers
Antioxidant spices reduce the formation of heterocyclic amines in fried meat
Zeitschrift f�r Lebensmitteluntersuchung und -Forschung A, 1998
Heterocyclic aromatic amines (HAs) are mutagenic compounds that are formed during heating of meat and fish. These substances are reaction products of creatine with amino acids and carbohydrates. It is recommended that exposure to these probable human carcinogens should be minimised. Five heterocyclic aromatic amines which occur in beef were investigated: , and 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP). Clean-up was done by acidbase partition followed by SPE using blue cotton. HPLC analysis was carried out by using electrochemical detection for IQ-and IQx-type compounds and fluorescence detection for PhIP. The concentrations of the aromatic amines were as follows: IQ, 10.2 mg/kg; MeIQ, 2.46 mg/kg; MeIQx, 13.2 mg/kg; 4,8-DiMeIQx, 2.26 mg/ kg; and PhIP, 5.48 mg/kg. The application of spices (rosemary, thyme sage, garlic, brine) reduced the content of the HAs below 60% of the amount found in the control.
Food and Chemical Toxicology, 2003
An association between the intake of heterocyclic amines (HAs) and the development of cancer has been observed in some epidemiological studies, while in other studies no such correlation has been found. HAs are mutagenic/carcinogenic compounds formed at low levels via the Maillard reaction and a free radical mechanism during cooking of animal tissue. The addition of pure antioxidants or foods containing antioxidants has previously been shown to decrease the amount of HAs formed during cooking. In this study, beefburgers were fried in six different oils: refined olive oil, virgin olive oil, virgin olive oil depleted of phenols, rapeseed oil, virgin olive oil with rosemary extract and refined olive oil with rosemary extract. The content of antioxidative compounds in the virgin olive oil and the rosemary extract was determined. The beefburgers were analysed with regards to 12 different HAs by solid phase extraction and HPLC analysis. MeIQx, 4,8-DiMeIQx, PhIP, Harman and Norharman were detected in all beefburgers fried in the different oils, but the relative amounts varied. Frying in virgin olive oil reduced the formation of HAs compared with refined olive oil. This effect is probably due to the content of phenols in the virgin olive oil. The HA-reducing effect of virgin olive oil decreased during storage, but the addition of rosemary extract may prevent this decrease. #
Journal of Agricultural and Food Chemistry, 2001
Mutagenic heterocyclic amines (HAs) are formed at low levels during cooking of meat and fish, and some of them are considered to be possible human carcinogens. The formation of HAs may be affected by the presence of synthetic or naturally occurring antioxidants. In the present study the effect of virgin olive oil (VOO) phenolic compounds, identified and quantified by LC-MS, on the formation of HAs in a model system was evaluated. An aqueous solution of creatinine, glucose, and glycine was heated in the presence of two samples of VOO differing only in the composition of phenolic compounds. The addition of VOO to the model system inhibited the formation of 2-amino-3methylimidazo[4,5-f]quinoxaline (IQx), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) by between 30 and 50% compared with the control. Fresh-made olive oil, which contained a high amount of dihydroxyphenylethanol derivatives, inhibited HA formation more than a 1-year-old oil did. The inhibition of HA formation was also verified using phenolic compounds extracted from VOO.
Phenolics: blocking agents for heterocyclic amine-induced carcinogenesis
Food and Chemical Toxicology, 1999
SummaryÐChemopreventive eects of synthetic and naturally occurring antioxidants on heterocyclic amine (HCA)-induced rat carcinogenesis and mechanisms of inhibition were assessed. In a medium-term liver bioassay, combined treatment with 0.03% 2-amino-3, 8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and synthetic antioxidants such as 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), butylated hydroxyanisole (BHA), butylated hydroxutoluene (BHT), tert-butylhydroquinone (TBHQ) or propyl gallate, each at a dose of 0.25%, inhibited development of preneoplastic glutathione S-transferase placental form (GST-P) positive foci as compared with MeIQx alone, after initiation with diethylnitrosamine (DEN). Of these antioxidants, HTHQ showed the greatest activity. 8-Hydroxydeoxyguanosine (8-OHdG), a marker for DNA damage induced by active oxygen species, and malonedialdehyde and 4-hydroxynonenal levels were not largely in¯uenced by the treatment with MeIQx or antioxidants, either alone or in combination. In the same medium-term liver bioassay, eects of some naturally occurring antioxidants, such as green tea catechins (GTC), hesperidin, chlorogenic acid, quercetin, rutin, curcumin, daidzin, ferulic acid and genistein were also examined. Of these antioxidants, only GTC tended to inhibit GST-P positive foci development, while quercetin, rutin, curcumin, daidzin, ferulic acid and genistein all exerted signi®cant enhancing eects. Examination of HTHQ in¯uence in a medium term liver bioassay with HCA Glu-P-1, in which the experimental period was extended for up to 26 weeks, also demonstrated a signi®cant decrease in the incidence of liver tumours to 40% in the group treated with 0.5% HTHQ and 0.03% 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) as compared with the Glu-P-1 alone value of 89%. Eects of HTHQ on colon carcinogenesis induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) were evaluated in a two-stage colon carcinogenesis model using 1,2-dimethylhydrazine (DMH) as an initiator. At week 36, the multiplicity of colon tumours induced by 0.02% PhIP after DMH initiation (9.126.2/rat) was dose-dependently decreased by the combined treatment with 0.5% HTHQ (3.621.8, P < 0.001) and 0.125% HTHQ (6.22 3.2, not signi®cant). Similarly, the incidence of mammary carcinomas in female F344 rats induced by oral administration of 0.02% PhIP (40%) for 52 weeks was signi®cantly decreased by simultaneous treatment with 0.5% HTHQ (5%). a-Tocopherol and chlorophyllin only reduced the multiplicity of carcinomas. Analysis of the in¯uence of HTHQ on metabolic activation of Glu-P-1 or PhIP after incubation with rat S9 mixture and NADPH by HPLC, revealed that each major metabolite was strongly reduced by the addition of HTHQ. Immunohistochemically detected PhIP±DNA adduct positive nuclei in the colon induced by continuous oral treatment with 0.02% PhIP for 2 weeks decreased by the combined treatment with 0.5 or 0.125% HTHQ. These results indicate that synthetic antioxidant HTHQ is a very strong chemopreventor of heterocyclic amine (HCA)-induced carcinogenesis and that depressed metabolic activation rather than antioxidant activity is responsible for the observed eect. # Abbreviations: AaC = 2-amino-9H-pyrido[2,3-b]indole; BHA = butylated hydroxyanisole; BHT = butylated hydroxutoluene; DEN=diethylnitrosamine; DMH=1,2-dimethylhydrazine; Glu-P-1=2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole; Glu-P-2 = 2-aminodipyrido[1,2-a:3',2'-d]imidazole; GST-P = glutathione S-transferase placental form; GTC = green tea catechins; 4-HNE = 4-hydroxynonenal; HCA = heterocyclic amine; HTHQ = 1-O-hexyl-2,3,5-trimethylhydroquinone; IQ = 2-amino-3methylimidazo[4,5-f]quinoline; MDA = malondialdehyde; MeAaC = 2-amino-3-methyl-9H-pyrido[2,3b]indole; MeIQ = 2-amino-3,4-dimethylimidazo[4,5-f]quinoline; MeIQx = 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline; PhIP = 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine; 8-OHdG = 8-hydroxydeoxyguanosine; TBHQ = tert-butylhydroquinone; Trp-P-1 = 3-amino-1,4-dimethyl-5H-pyrido[4,3b]indole; Trp-P-2 = 3-amino-1-methyl-5H-pyrido[4,3-b]indole.
Cancer Letters, 1994
Results in the Carcinogenic Potency Database (CPDB) on 11 mutagenic heterocyclic amines (HA) tested for carcinogenicity in rats, mice and cynomolgus monkeys are compared to results for other chemicals. An analysis of strength of evidence of carcinogenicity for HA vs. other mutagenic carcinogens and vs. all rodent carcinogens, indicates strong carcinogenicity of HA in terms of positivity rates and multiplicity of target sites. The liver is the most frequent target site in each species. Despite several target sites in each species, concordance in target sites between rats and mice is restricted to the liver for each HA except one. In cynomolgus monkeys, liver tumors have been induced rapidly by 2-amino-3-methylimidazo[4,5#Jquinoline (IQ). Human exposures to HA in cooked animal foods are small, in the Iow ppb range. A comparison of possible carcinogenic hazards from a variety of exposures to rodent carcinogens in the American diet is presented, using an index (Human Exposure/Rodent Potency, HERP) that relates human exposure to carcinogenic potency in rodents. Results indicate that there is a large background of exposures to naturallyoccurring rodent carcinogens in typical portions of common foods, and that possible hazards from HA rank below those of most natural pesticides and products of cooking or food preparation; synthetic pesticide residues also rank low.
1996
Muscle foods, when cooked, sometimes form heterocyclic amines that are mutagenic in bacteria and carcinogenic in animal tests. A survey of commercially cooked meats from restaurants or grocery stores reflected varying levels from undetectable to 560 revertant colonies per gram in the Salmonella strain TA98 mutagenicity test. Home and laboratory cooked meats revealed up to 4000 TA98 revertants per gram of cooked meat. Heterocyclic amine mutagens/carcinogens responsible for the mutagenic activity were detected in some samples at 1.5 to 400 ppb. Since these compounds are formed from natural components in meats during heating, the cooking time and temperature are determinants for their production. Clearly, cooking conditions can be modified to greatly reduce or eliminate these carcinogens from our diet.
EVALUATION OF MUTAGENIC POTENTIALITY OF Heterocyclic Amines EXTRACTed from COOKED CHICKENs
Several evidences indicated that diet and dietary behaviors can contribute to human cancer risk. One way is this occurs through the ingestion of food mutagens. Heterocyclic amines (HCAs) are important class of food mutagens and carcinogens, which can be found in cooked meat, chicken and fish. The presence of these mutagens and their types is dependant on cooking method, heating temperatures and time of cooking. In this study, the effect of cooking method (frying, broiling and microwave-cooking as conventional and unconventional cooking methods) on formation of food mutagen(s) in Egyptian cooked chicken was studied using three short-term mutagenicity assays; yeast D7, somatic mutation and recombination test in Drosophila and rat bone marrow chromosomal aberrations assay. Mutagenic/carcinogenic heterocyclic amines (HCAs) are formed at low levels (ng/g) during heat processing of protein-rich food, therefore blue rayon was used as effective extraction and purification method. The results of mutagenicity bioassays indicated that all used cooking methods in this study were capable of forming food mutagen(s) and gave positive significant mutagenic effects in all tested assays. The cooked chicken extracts could be arranged according to their mutagenic potentiality as: fried chicken > microwave-cooked chicken > vertical gas broiled chicken.
Chemoprevention of heterocyclic amine-induced carcinogenesis by phenolic compounds in rats
Cancer Letters, 1999
Chemopreventive effects of synthetic and naturally occurring antioxidants on heterocyclic amine (HCA)-induced rat carcinogenesis and mechanisms of inhibition were assessed. In a medium-term liver bioassay, combined treatment with 0.03% 2amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and synthetic antioxidants such as 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), BHA, BHT, tert-butylhydroquinone (TBHQ) and propyl gallate, each at a dose of 0.25%, and troglitazone at doses 0.5 and 0.1%, potently inhibited development of glutathione S-transferase placental form (GST-P) positive foci as compared with MeIQx alone values. Of these antioxidants, HTHQ showed the greatest activity. Green tea catechins tended to inhibit GST-P positive foci development, while quercetin, rutin, curcumin, daidzin, ferulic acid and genistin all exerted signi®cant enhancing effects. HTHQ also inhibited 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced colon carcinogenesis in a two stage colon carcinogenesis model using 1,2-dimethylhydrazine (DMH) as an initiator. Immunohistochemically detected PhIP±DNA adduct positive nuclei in the colon induced by continuous oral treatment with 0.02% PhIP for 2 weeks decreased by the combined treatment with 0.5 or 0.125% HTHQ. Methoxyresor®n O-demethylase activity in rat liver microsomes in vitro was clearly inhibited by the addition of HTHQ, BHA, BHT, TBHQ or propyl gallate, with particularly strong inhibition being observed in HTHQ. However, the CYP1A2 level in rat liver increased after oral treatment with HTHQ for 2 weeks. These results indicate that synthetic antioxidants, HTHQ in particular, is a very strong chemopreventor of HCAinduced carcinogenesis. It is suggested that depression of metabolic activation rather than antioxidant activity is responsible for the observed effect. However, other mechanisms, including the effects on phase II enzymes cannot be ruled out. q
Production of heterocyclic aromatic amines in meat: Chemistry, health risks and inhibition. A review
Heterocyclic aromatic amines are compounds produced in meat subjected to high temperature cooking. Formation of these substances is highly influenced by cooking method, cooking time, cooking temperature, and type of meat. Heterocyclic amines contain heterocyclic rings and nitrogen containing groups within their structure. Risks of colon, pancreas, gastrointestinal tract, lung, liver, prostate, skin and breast cancers are decidedly associated with the consumption of heterocyclic amines. These mutagenic compounds can be attenuated by addition of different fruits and vegetable extracts. Several spices and antioxidants can also be used for the reduction of these heterocyclic amines. The level of heterocyclic amines can be reduced by cooking at low temperature and by decreasing the cooking time. Formation of heterocyclic amines can also be prevented by marinating the meat before frying or grilling and by microwave pre-treatments. Objectives of this review are to create awareness about health risks, and to stimulate further research on other suitable ways to reduce the cancer risks associated with the consumption of cooked meat products.
Foods
Heterocyclic aromatic amines (HAAs) are potent carcinogenic compounds induced by the Maillard reaction in well-done cooked meats. Free amino acids, protein, creatinine, reducing sugars and nucleosides are major precursors involved in the production of polar and non-polar HAAs. The variety and yield of HAAs are linked with various factors such as meat type, heating time and temperature, cooking method and equipment, fresh meat storage time, raw material and additives, precursor’s presence, water activity, and pH level. For the isolation and identification of HAAs, advanced chromatography and spectroscopy techniques have been employed. These potent mutagens are the etiology of several types of human cancers at the ng/g level and are 100- to 2000-fold stronger than that of aflatoxins and benzopyrene, respectively. This review summarizes previous studies on the formation and types of potent mutagenic and/or carcinogenic HAAs in cooked meats. Furthermore, occurrence, risk assessment, and...