PubMed Health⌕ Search

Biomedical subjects

M D Friesen

Publications and source records attributed to M D Friesen.

29 records · Page 2Linked to original sources

Urinary markers for measuring exposure to endogenous and exogenous alkylating agents and precursors.

Noninvasive methodologies for measuring carcinogen exposure in humans, based on the use of urinary markers, are being developed and validated for use in molecular epidemiological studies. A range of 3-alkyladenines can be determined in urine samples by an immunoaffinity purification-GC/MS approach [3-methyladenine, 3-ethyladenine, 3-(2-hydroxyethyl)adenine, and 3-benzyladenine]. Using this method, recent results in human subjects suggest that urinary 3-alkyladenines are potentially useful markers of alkylating agent exposure, particularly where the backgrounds of such adducts are much lower than 3-methyladenine. Urinary excretion of S-benzylmercapturic acid has been studied in experimental animals as a marker of exposure to benzylating agents such as N-nitroso-methylbenzylamine. 3-Nitrotyrosine (NTyr) is formed in vivo in tissue or blood proteins after exposure to nitrosating and/or nitrating agents such as tetranitromethane. After turnover of proteins, NTyr is released and excreted in urine as metabolites 3-nitro-4-hydroxy-phenylacetic acid and 3-nitro-4-hydroxyphenylacetic acid, which are determined by GC with a thermal energy analyzer. The sensitivity and specificity, combined with ease of use, of these noninvasive biomonitoring approaches means that they may be readily incorporated into molecular epidemiological studies in which exposure to nitrosating and alkylating agents may be important risk factors.

Acetylcysteine↗

A rapid gas chromatography-mass spectrometry method for the determination of urinary 3-methyladenine: application in human subjects.

A rapid gas chromatography-mass spectrometry method, employing immunoaffinity clean-up, has been developed for the measurement of 3-methyladenine in human urine samples. A wide variation in levels of urinary 3-methyladenine was observed, indicating that at least some may be derived from the diet and not be related to endogenous nitrosation and subsequent methylation.

Adenine↗

N-nitrosamines and nitrosatable amines, potential precursors of N-nitramines, in children's pacifiers and baby-bottle nipples.

Sixteen types of children's pacifiers and baby-bottle nipples, bought in shops in Israel but produced both there and elsewhere in the world, were analyzed for their contents of N-nitrosamines, which have been shown to be potent carcinogens in animals, and of nitrosatable amines. Two methods were used: one, originating in the United States, involved dichloromethane extraction of total volatile N-nitrosamines from the nipples and pacifiers, and the other, from the Federal Republic of Germany, consisted of analysis of N-nitrosamines and their amine precursors that migrated into artificial saliva. N-Nitrosodibutylamine (NDBA). N-nitrosodiethylamine (NDEA), N-nitrosodimethylamine (NDMA). N-nitrosopiperidine (NPIP), and N-nitrosopyrrolidine (NPYR) were detected by the first method, at individual levels as high as 369 ppb. Using the second method, NDBA, NDEA, NDMA, and N-nitrosomorpholine (NMOR) were detected at concentrations up to 41 ppb, in addition to the three nitrosatable amines dibutylamine, diethylamine, and dimethylamine. Upon nitrosation in the artificial saliva, these amines produced not only the related N-nitrosamines but also relatively high levels of the corresponding N-nitramines (N-nitrodibutylamine, N-nitrodiethylamine, and N-nitrodimethylamine), probably formed by oxidation of the N-nitrosamines by peroxides used for vulcanization of elastomers. Thus, if N-nitramines are not measured in addition to N-nitrosamines after nitrosation, the second method may underestimate the quantities of nitrosatable amines present in artificial saliva extracts. Whether N-nitramines, some of which have been shown to be both mutagenic and carcinogenic, also occur in the saliva of babies exposed to these products remains to be confirmed. Of the samples tested, 50% failed to meet both the U.S. and the FRG regulations. A larger percentage, 60%, would not conform to the new standard suggested in the United States, and more than 80% failed to comply with the even stricter Dutch standard.

Amines↗

International mycotoxin check sample survey program. Part III. Report on performance of participating laboratories for determining ochratoxin A in animal feed.

A sample of animal feed made from barley, naturally contaminated at about 1000 micrograms ochratoxin A/kg, was analyzed by 44 laboratories in 24 countries. The AOAC method for determining ochratoxin A in barley was used by 27 (61%) of the participating laboratories. Results from laboratories using this method were grouped around 2 maxima: one below 100 micrograms/kg and a second near 940 micrograms/kg, the median concentration for results reported by all 44 participating laboratories. Results from laboratories using methods other than the AOAC method were more widely distributed with no apparent maximum near 1000 micrograms/kg.

Animal Feed↗

International mycotoxin check sample program: Part I. Report on laboratory performance for determination of aflatoxins B1, B2, G1, and G2 in raw peanut meal, deoiled peanut meal, and yellow corn meal.

Three aflatoxin-contaminated samples (raw peanut meal, deoiled peanut meal, and yellow corn meal) were analyzed by 121 laboratories in 31 countries. Sufficient data were obtained to permit a statistical comparison of the performance of laboratories using the BF, CB, and EEC methods and those using high performance liquid chromatography (HPLC) for quantitation. No significant differences were found between means for laboratories using these 4 methods for the analysis of raw peanut meal or yellow corn meal. However, for deoiled peanut meal, means were significantly different for laboratories using the BF method compared with the CB or EEC methods for B1 and B2, and for laboratories using the CB method compared with HPLC methods for G2.

Aflatoxin B1↗

International mycotoxin check sample program: Part II. Report on laboratory performance for determination of aflatoxin M1 in milk.

A sample of aflatoxin M1-contaminated lyophilized cow's milk was analyzed by 80 laboratories in 30 countries. Sufficient data were obtained to permit a statistical comparison of the performance of laboratories using AOAC methods I and II and those using high performance liquid chromatography for quantitation. A significant difference was noted between means for laboratories using AOAC method I as opposed to those using HPLC methods. Overall reproducibility (between- plus within-laboratory precision) was best for laboratories using HPLC methods and poorest for those using AOAC method II.

Aflatoxin M1↗

Mass spectrometry of di-(2-ethylhexyl)phthalate metabolites.

The electron impact, methane positive chemical ionization, oxygen negative chemical ionization and collision induced dissociation mass analyzed ion kinetic energy spectra of nine metabolites of di-(2-ethylhexyl)phthalate are presented. The collision induced dissociation mass analyzed ion kinetic energy spectra of selected fragment ions were useful for structural information.

Animals↗

International mycotoxin check sample program. Part I. Report on the performance of participating laboratories.

Three aflatoxin-contaminated samples, raw peanut meal, finished peanut butter, and white corn meal, were analyzed by 139 laboratories in 34 countries. Sufficient data were obtained to permit a statistical comparison of the performance of laboratories using the BF, CB, and Pons methods and those using high performance liquid chromatography for quantification. A raw peanut meal sample showed no significant differences among means for laboratories using the four methods, and a white corn meal sample showed only one such significant difference; however, a finished peanut butter sample containing less than 10 micrograms total aflatoxins/kg showed 10 significant differences among means for laboratories using the 4 methods considered.

Aflatoxins↗

Isolation of urinary 3-methyladenine using immunoaffinity columns prior to determination by low-resolution gas chromatography-mass spectrometry.

An ammonium sulfate precipitated immunoglobin G (IgG) fraction from rabbit antiserum, prepared by use of novel haptenic derivatives, was used to make immunoaffinity columns for purification of 3-methyladenine (3-MeAde) from human urine. IgG was covalently bound to protein A-Sepharose, and the resulting affinity gel columns were sufficiently stable for multiple reuse. 3-MeAde (up to 200 ng) was adsorbed at pH 7.4 and, after extensive washing, eluted with 1 M acetic acid. Recovery of 3-MeAde was typically greater than 90%. For gas chromatography-mass spectrometry analysis, deuterium-labeled (d3) 3-MeAde (50 ng per sample) was used as an internal standard. 3-MeAde was determined as the mono-tert-butyldimethylsilyl derivative and quantitated by measurement of ions at m/z 206 (3-MeAde-d0) and m/z 209 (3-MeAde-d3). Repeated analyses of a human urine sample show excellent reproducibility of the method.

Adenine↗

Analysis of DNA adducts of 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine in rat and human tissues by alkaline hydrolysis and gas chromatography/electron capture mass spectrometry: validation by comparison with 32P-postlabeling.

A sensitive and specific method has been developed to measure levels of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) adducted to DNA in tissues. The method is based on alkaline hydrolysis of PhIP from DNA, followed by organic solvent extraction, derivatization to form the electron-capturing bis(pentafluorobenzyl) derivative, and analysis by gas chromatography/electron capture mass spectrometry (GC/MS) using a deuterium-labeled internal standard. The method can detect PhIP-DNA adducts at levels down to 0.03 fmol of PhIP/micrograms of DNA (1 PhIP adduct/10(8) normal nucleotides) for a 100 micrograms sample of DNA. The method is reproducible for sample sizes ranging up to at least 1000 micrograms of DNA. A series of 20 DNA samples from 5 tissues of rats treated with a single oral dose of PhIP were analyzed both by alkaline hydrolysis-GC/MS and by 32P-postlabeling. Results from the two methods were highly correlated (r2 = 0.83), with adduct levels determined by alkaline hydrolysis-GC/MS averaging about 60% of the levels determined by 32P-postlabeling. A pilot survey of 24 individual human tissue DNA samples, including pancreas (n = 12), colon mucosa (n = 6), and urinary bladder epithelium (n = 6), was carried out by alkaline hydrolysis-GC/MS and 32P-postlabeling. Both methods provided evidence for PhIP-DNA adducts in two of the colon samples, but not in the samples from human pancreas or urinary bladder.

Animals↗