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M Jägerstad

Publications and source records attributed to M Jägerstad.

At least 19 recordsLinked to original sources
PubMed1992

Formation of new heterocyclic amine mutagens by heating creatinine, alanine, threonine and glucose.

A mixture of alanine, threonine, creatinine and glucose was heated in diethylene glycol and water (5:1, v/v) for 15 min at 200 degrees C. The mutagens formed were purified by high-performance liquid chromatography using the Ames/Salmonella mutagenic activity to guide the purification. The structures of the purified mutagens were determined using UV absorption, mass and NMR spectrometry. A new mutagenic compound with a mass number of 217 was found and its mass spectrum did not correspond to any known mutagen derived from food. This new compound accounted for 4% of the total mutagenic activity. Other mutagenic compounds were identified as MeIQx (2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline), 4,8-DiMeIQx (2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline), and a new mutagen 4,7,8-TriMeIQx (2-amino-3,4,7,8-tetramethylimidazo[4,5-f]quinoxaline) with a mutagenic activity of 73,000 TA98 revertants per microgram. The percentage of the mutagenic activity attributable to MeIQx, 4,8-DiMeIQx and 4,7,8-TriMeIQx was 10%, 70% and 3%, respectively. The yield of MeIQx, 4,8-DiMeIQx and 4,7,8-TriMeIQx was 10, 36 and 6 nmole/mmole creatinine. The formation of TriMeIQx from natural meat components suggests that this new quinoxaline mutagen may be present in cooked foods.

Alanine↗
PubMed1992

Inhibitory effect of carbohydrates on the formation of mutagens in fried beef patties.

Beef patties were prepared by mixing minced meat with water and either glucose (1, 2 or 4%), lactose (1, 2 or 4%) or powdered milk (2, 4 or 8%) before frying. In another experiment, minced meat was mixed with starch from golden bread crumbs (3%) or potatoes (4%), with and without glucose (1, 2 or 4%). The patties (100 g) were fried for 3 min at 150 or 180 degrees C in a double-sided fryer. The mutagenic activity in the crust was determined using the Ames test. With the addition of glucose or lactose (1-4%), the mutagenic activity was inhibited by 34-76%. A similar inhibition of the mutagenic activity was obtained with powdered milk. However, starch from golden bread crumbs or potatoes caused only a slight (not significant) decrease in mutagenic activity whereas adding both starch and glucose to the beef patties inhibited mutagenic activity by up to 54%.

Animals↗
PubMed1992

Effect of dietary fiber on the disposition and excretion of a food carcinogen (2-14C-labeled MeIQx) in rats.

We studied to what extent dietary fiber may affect uptake, retention, and excretion of a food carcinogen (2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, MeIQx) occurring in fried meat. Four diets--one fiber-free control and three containing either insoluble dietary fiber isolated from sorghum (100 g/kg) and wheat bran (100 g/kg) or the highly soluble pectin (50 g/kg)--were investigated. The fiber diets were given in amounts of 10 g/day to rats. Thus, each rat received 1 or 0.5 g fiber and 100 micrograms 2-14C-labeled MeIQx uniformly mixed in its daily diet. A 4-day adaptation period with unlabeled MeIQx was followed by a 5-day experimental period with 14C-labeled MeIQx, during which urine and feces were collected separately for analysis of radioactivity and mutagenicity. Furthermore the composition and the fermentability of the dietary fiber were determined. The present study shows that a diet containing fiber, especially fiber isolated from sorghum and wheat bran, affects the excretion pattern of the food carcinogen MeIQx in a manner suggesting a lower uptake and a decreased transit time through the gastrointestinal tract in a more diluted form than a nonfiber diet. Furthermore, less radioactivity was retained in the kidneys with sorghum and wheat bran than with the other two diets. On the other hand, none of these types of dietary fiber affected the retention of the hepatocarcinogen MeIQx in the liver 24 hours after the last oral intake. DNA adducts were formed to a higher extent in the kidney than in the liver. The highest levels were found in animals given the wheat bran diet.

Animals↗
PubMed1991

Formation of meat mutagens.

The formation of meat mutagens has been studied the last 10 years by carrying out modeling and meat cooking experiments in parallel. During this time, the list of meat mutagens has been growing, and continues to grow. The meat mutagens are usually produced in the crust of animal foods during frying, broiling, and baking. Another important source is meat extracts, consumed as gravies and meat bouillons. The formation of meat mutagens has been shown to depend physically on time, temperature, and water. Three major precursors have been identified: creatine or creatinine, certain amino acids, and monosaccharides or disaccharides. A requirement of sugar assumes a participation of the Maillard reaction, which also forms the basis for one of the major reaction mechanisms suggested. However, the meat mutagens are produced also in the absence of sugars, which means that other routes might be possible as well. Although the major precursors have been identified, more work needs to be done on the reaction mechanisms, the kinetics, and on the food constituents that might enhance or inhibit the formation of the meat mutagens. The results obtained to date point to several possibilities to control the formation of meat mutagens.

Animals↗
PubMed1991

Effects of glucose on the formation of PhIP in a model system.

The effect of glucose on the formation of the food mutagen PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) was studied in a model system. When a mixture of creatine (0.9 mmol), phenylalanine (0.9 mmol) and glucose (0.45 mmol) was heated in diethylene glycol and water (3 ml, 5:1) for 10 min at 180 or 225 degrees C several mutagens were produced. Identification by HPLC, UV absorption spectroscopy and mass spectrometry revealed the presence of PhIP as well as 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline and minor amounts of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline. Heating the system without glucose produced PhIP as a single mutagen, but in considerably lower amount. An inhibiting effect of glucose in high concentrations was demonstrated. When glucose was added in more than or equimolar amounts of the other two reactants, the formation of mutagens was markedly reduced. Tyrosine heated under the same conditions, with creatine and glucose, showed mutagenic activity. However, no PhIP nor any other known food mutagen was identified from the tyrosine mixture.

Creatine↗
PubMed1990

Effects of monosaccharides and disaccharides on the formation of food mutagens in model systems.

The formation of the mutagenic imidazoquinoxalines (MeIQx, DiMeIQx) was studied using a modification of a previous model system. Creatine or creatinine (0.9 mmole) was heated together with glycine (0.9 mmole) and various sugars (0.45 mmole) dissolved in diethylene glycol and water (3 ml, 5:1) for up to 15 min at 180 degrees C. This system produced the same amount of mutagenicity after 10 min at 180 degrees C as a previous one during 2 h of reflux boiling at 128 degrees C. MeIQx (4 nmole/mmole creatin(in)e) was the major mutagen produced together with minor amounts of DiMeIQx, both 4,8- and 7,8-DiMeIQx according to HPLC-MS. A few other mutagenic peaks were also separated on HPLC, but they were not identified. Varying the concentration (0-2.4 mmole) and type of monosaccharides and disaccharides greatly affected the yields of all the mutagenic compounds. Sugar in molar amounts lower than the creatin(in)e concentration increased the yield until an optimum was reached. In higher concentrations the formation of all the mutagens was markedly reduced. The same was found for glucose, fructose, sucrose, and lactose, though the monosaccharides showed the most pronounced inhibitory effects. The inhibition of the formation of the mutagenic compounds by an excess of sugars is proposed to be an effect of Maillard reaction products, which may block the formation of imidazoquinoxalines by attacking creatine. Support for this mechanism is given by data showing a lower recovery of unreacted creatine with increasing concentration of glucose and also by an inhibitory effect on the formation of these mutagens after adding a typical Maillard reaction product, 5-hydroxymethyl-2-furfural.

Chromatography, High Pressure Liquid↗
PubMed1989

Disposition and metabolism of the food mutagen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in rats.

The disposition and metabolism of a common food mutagen, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), was studied in rats. Five rats of both sexes were given a single oral dose of 14C-labeled MeIQx (3-4 mg/kg body wt). The male rats excreted 36% of the radioactivity and 15% of the mutagenic activity of the dose given in the urine collected during the first 24 h. In the females the corresponding urine contained 41% of the radioactivity and 12% of the mutagenicity. During the next 48 h only 1-3% of the radioactive dose was excreted in urine. The remaining dose was excreted in the feces except of less than 1% that was retained by the tissues after 72 h. The liver and kidney retained more radioactivity than other organs. In a separate study the metabolites of bile, urine and feces of both sexes were investigated. After a single oral dose of 20 mg 14C-labeled MeIQx/kg body wt, three major non-mutagenic metabolites were identified. These were 2-amino-4(or 5)-(beta-D-glucuronopyranosyloxy)-3,8-dimethylimidazo[4,5-f] quinoxaline, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxalin-4(or 5)-yl sulfate and N-(3,8-dimethylimidazo[4,5-f]quinoxalin-2-yl) sulfamate. Another two metabolites present in bile, urine and feces were 2-(beta-D-glucuronopyranosylamino)-3,8-dimethylimidazo[4,5-f ] quinoxaline and 2-amino-8-hydroxymethyl-3-methylimidazo[4,5-f]quinoxalin-4 (or 5)yl sulfate. All metabolites were essentially non-mutagenic. Most of the mutagenicity still present in bile, urine and feces could be explained by unchanged MeIQx. Unchanged MeIQx was the most abundant form excreted in urine.

Animals↗
PubMed1988

Cereal fructans: in vitro and in vivo studies on availability in rats and humans.

The bioavailability of cereal fructans (fructooligosaccharides) was investigated both in vitro and in vivo. In vitro studies indicated very slow hydrolysis by human gastric juice and by homogenate of the intestinal mucosa (rat). After intubation of fructans into the stomachs of rats, the recovery of fructans in the small intestine and colon was approximately the same as that of an unabsorbed marker (polyethylene glycol), indicating no or very low disappearance of fructans in the small intestine. In vivo studies of the small intestine in rats showed that the rate of disappearance of fructans was lower than that of mannose, which is known to be absorbed through passive diffusion. In addition the cariogenic effect of cereal fructans was compared to that of glucose. Acid formation from low molecular-weight fructans was found in human dental plaque in vitro. A mouth rinse with unfractionated fructans, containing some quantities of sucrose, fructose and glucose, resulted in relatively low pH values in human plaque in vivo, even if the decrease in pH was somewhat less pronounced when compared with a mouth rinse with glucose.

Adult↗
PubMed1987

Effects of creatine and creatinine content on the mutagenic activity of meat extracts, bouillons and gravies from different sources.

Thirteen commercial meat-flavour samples were analysed for creatine and creatinine content and tested for mutagenicity in the Ames Salmonella/microsome test. In most samples, more than 50% of the creatine had been converted to creatinine. Mutagenicity was related to the creatinine content: 150 mumol creatinine/g dry matter (gdm) gave upwards of 2500 revertants/gdm, concentrations of 15-40 mumol/gdm gave about 100 revertants/gdm and concentrations of 1-10 mumol/gdm gave only low or no significant mutagenicity. No relationship was apparent between coloration and mutagenicity. Beef steaks (initial weight c. 500 g) baked at oven temperatures between 115 and 245 degrees C only showed significant mutagenicity--135 revertants/100 gE (initial raw weight)--in the crust when baked at the highest temperature (245 degrees C). The gravies (meat-juice drip) collected during baking showed a linear increase in mutagenicity with baking temperatures up to 180 degrees C (48-828 revertants/100 gE) and a very sharp increase in mutagenicity for the gravy collected from beef steak baked at 245 degrees C (28,300 revertants/gdm or 19,800 revertants/100 gE). At this high temperature, the brown coloration and the proportion of creatinine to total creatine and creatinine were also dramatically increased, because this gravy dried up completely during the baking procedure.

Animals↗
PubMed1987

Mutagenicity of pan-fried bovine tissues in relation to their content of creatine, creatinine, monosaccharides and free amino acids.

The mutagenicity of pan-fried patties of five bovine tissues (meat, heart, tongue, liver and kidney) containing various concentrations of creatine, monosaccharides and free amino acids were studied. Two experiments were performed, one on single tissues fried at 150, 175 or 200 degrees C for 3 min and the other on mixtures of meat and one of the other four tissues in various proportions, fried at 200 degrees C for 3 min. For both experiments, a double-sided Teflon-coated plate was used. Frying at 150 degrees C induced mutagenicity to Salmonella typhimurium strain TA98 only in the heart sample-6000 revertants/100 gE (grams initial raw weight). Meat, heart and tongue fried at 175 or 200 degrees C showed mutagenicity values between 6000 and 19,600 revertants/100 gE. A linear relationship between mutagenicity and temperature was obtained for each of the three muscles and creatine was converted to creatinine with increasing temperature. Liver or kidney samples fried alone showed insignificant mutagenicity at all three temperatures. The creatine plus creatinine levels of raw meat, heart and tongue samples were between 19 and 33 mumol/g wet tissue. Liver and kidney both showed very low amounts of creatine plus creatinine (about 2 mumol/g wet tissue) in the raw tissue, while free amino acids were high. Glucose levels were high in liver but low in kidney samples. In meat/heart and meat/tongue mixtures the mutagenicity varied between 10,800 and 17,300 revertants/100 gE. The meat/liver and meat/kidney mixtures showed linear relationships between mutagenicity and the proportions of the mixture. The values for the slopes and intercepts of the two lines were almost equal. Among the three groups of precursors (creatine plus creatinine, monosaccharides and free amino acids) the creatine plus creatine in raw tissue seems to be the most important for producing mutagenicity. However, in crusts, the creatinine concentration was the variable with which most of the mutagenicity was associated.

Amino Acids↗
PubMed1987

Hydrolysis of lactitol, maltitol and Palatinit by human intestinal biopsies.

1. The hydrolysis of sugar alcohols of the disaccharide type such as lactitol, maltitol and Palatinit (the latter an equimolar mixture of 6-O-alpha-D-glucopyranoside-D-mannitol and 6-O-alpha-D-glucopyranoside-D-sorbitol) by homogenates of human intestinal biopsies were compared with corresponding natural disaccharides such as lactose, maltose and isomaltose. Seven of the human biopsies were normal with regard to their disaccharidase activities, while twelve biopsies showed decreased levels of disaccharidase activities. 2. All biopsies, normal as well as abnormal, showed essentially the same capacity to hydrolyse the sugar alcohols. Activities towards lactitol (0.34 IE/g protein (where IE = mumol disaccharide hydrolysed/min at 37 degrees)) and Palatinit (2.50 IE/g protein) were only 1.3% of those towards lactose and isomaltose. The activity towards maltitol was much higher (19.1 IE/g protein), approximately 10% of that towards maltose and about as high as the activity towards trehalose. This finding indicates that despite the fact that lactitol and Palatinit were poor substrates, significant amounts of ingested maltitol might be digested and utilized by man. 3. Glucose release was reduced by approximately 25% when maltitol or Palatinit were present at concentrations equal to those of maltose. Palatinit decreased the hydrolysis of sucrose by 12%. Lactitol had no inhibitory effect on the hydrolysis of disaccharides.

Adolescent↗
PubMed1986

Formation of 4,8-DiMeIQx from the model system fructose, alanine and creatinine. Comparison with the isomeric 5,8-DiMeIQx.

In a previous paper, the main mutagenic compound isolated from the model reaction system D-fructose, DL-alanine and creatinine was tentatively identified as 4,8-DiMeIQx. Its mutagenic activity and spectral characteristics have now been compared with those of the isomer 5,8-DiMeIQx. The comparison clearly demonstrates that the isolated compound was indeed 4,8-DiMeIQx. This finding is in agreement with the hypothesis that sugars, amino acids and creatinine present in meat may be the precursors of the mutagenic imidazoquinolin- and imidazoquinoxalin-2-amines (IQ compounds).

Alanine↗
PubMed1986

Iron, zinc and folate status during pregnancy and two months after delivery.

Iron, zinc and folate statuses of 45 women were determined during pregnancy around 12, 20, 28, 32 and 36 weeks, and again 2 months after delivery. Analyses of plasma ferritin, Hb, MCV, folate and zinc in plasma and whole blood were performed. Iron supplementation was recommended from mid-pregnancy but 13 of the participants did not use the iron supplements. This group had significantly decreased levels of plasma ferritin and MCV at the end of pregnancy, but none developed anemia. Two months post partum the plasma ferritin of the unsupplemented group had normalized and was in the same range as in the supplemented group. The concentrations of zinc in plasma and whole blood and the calculated levels of red cells were low even at the first examination around 12 weeks of gestation, compared with non-pregnant women. Throughout the course of pregnancy the plasma zinc levels continued to decrease, while the whole blood and red cell levels showed a significant rise. At term of gestation almost half the women had subnormal plasma folate levels (L. casei), which persisted during the post partum follow-up. The corresponding value for red cell folate was 10% below normal values at term and 30% subnormal 2 months after parturition. These findings stress the importance of extending the observation period to include also the lactating period, in order to judge the need for folate supplementation.

Adult↗
PubMed1985

Formation of a new mutagenic DiMeIQx compound in a model system by heating creatinine, alanine and fructose.

A mixture of creatinine, D-fructose and DL-alanine was heated in diethylene glycol containing 14% water for 2 h at ca. 128 degrees C. The mutagens formed were extracted with 1-butanol, and purified by cation-exchange column chromatography, C18 reversed-phase Sep-Pak treatment and reversed-phase HPLC. According to its UV absorption, mass and 1H NMR spectra, one isolated fraction was tentatively assigned the chemical name, 3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxalin-2-amine (4,8-DiMeIQx). This finding is in agreement with the suggestion that sugars, amino acids and creatinine present in meat may be the precursors of the mutagenic imidazoquinolin- and imidazoquinoxalin-2-amines (IQ compounds).

Alanine↗
PubMed1985

The synthesis and mutagenicity of the 3-ethyl analogues of the potent mutagens IQ, MeIQ, MeIQx and its 3,7-dimethyl isomer.

The title compounds were synthesized and tested for mutagenicity on Salmonella typhimurium TA98 in the presence of S9 mix. All test compounds showed lower activity than their respective 3-methyl analogues (IQ compounds). The replacement of the 3-methyl by an ethyl group should not alter the chemistry of these compounds; hence, their lower mutagenic activity could merely be of steric origin.

Imidazoles↗
PubMed1985

Effects of meat composition and cooking conditions on the formation of mutagenic imidazoquinoxalines (MeIQx and its methyl derivatives).

In recent years it has been shown that certain methyl derivatives of 3H-imidazo[4,5-f]quinoxaline-2-amine are responsible for a major part of the mutagenicity formed during frying, broiling or baking of meat, and also formed in the preparation of meat extracts. The present study describes the precursors of these compounds and their formation with participation of Maillard or nonenzymatic browning reactions. The formation of these IQ-type mutagens was shown to occur when model systems of creatin(in)e, reducing monosaccharides, and certain amino acids were heated at 128 degrees C for 2 hr. In meat experiments, the mutagenicity was found to be significantly correlated with the presence of creatin(in)e in the meat samples. The same conditions that are favorable for Maillard reactions, such as supply of starting materials, high temperature, and a suitable water concentration, also increased the yield of mutagenicity during cooking. Fats seemed to act as regulators of the amount of heat transferred into the product rather than as reactants in the formation of mutagenicity.

Amino Acids↗