Marlin Friesen - Academia.edu (original) (raw)
Papers by Marlin Friesen
Chemical Research in Toxicology, Aug 8, 2001
Carcinogenesis, 1982
Samples of opium pipe scrapings (opium dross, called sukhteh locally), but not of crude opium, co... more Samples of opium pipe scrapings (opium dross, called sukhteh locally), but not of crude opium, collected in an area with a high incidence of oesophageal cancer in north-east Iran, were shown to contain pro-mutagens, producing mostly frameshift mutations in Salmonella typhimurium strains TA1538 and TA98 after metabolic activation. Pyrolysis of opium and of its major alkaloid, morphine, yielded smoke condensates with mutagenic activities 10 and 100 times higher, respectively, than that of the sukhteh samples tested. Heterocyclic aromatic hydrocarbons and primary aromatic amines present at different concentrations in these three pyrolysates are considered to be the major active principles. Opium addiction has been implicated as a risk factor in bladder cancer in humans and the ingestion of opium pyrolysates, in conjunction with dietary deficiencies, may be related to the high incidence of oesophageal cancer in north-east Iran, although causality has not been established.
Investigative Ophthalmology & Visual Science, Dec 1, 2002
PubMed, 1987
A series of nine glycosylamines and an Amadori compound and their N-nitroso derivatives were synt... more A series of nine glycosylamines and an Amadori compound and their N-nitroso derivatives were synthesized. The structures were ascertained by spectroscopy and elemental analysis. The N-nitroso compounds were further characterized by denitrosation with hydrogen bromide-acetic acid, followed by detection of the liberated NO by a chemiluminescence detector. N-Nitroso derivatives of N-p-nitrophenyl/p-methylphenyl/p-carboxyphenyl pentosylamines, N-p-methylphenyl-1-deoxy-D-fructosylamine (Amadori compound) and N-3-ethylindole-D-xylosylamine were shown to be directly-acting mutagens in Salmonella typhimurium TA100. The activity of some of the compounds was similar to that of N-ethyl-N-nitrosourea. Their mutagenic activity was shown to be dependent on the structure of the amine and the sugar moieties and requires the presence of free hydroxyl groups in the sugar. The mutagenicity of N-nitrosoglycosylamines was attributed to their hydrolysis to arene diazonium cations. Their formation was detected via azo-coupling with N-ethyl-1-naphthylamine, using spectrophotometric and mass-spectrometric analyses. Our data implicate arene (alkyl) diazonium cations as the ultimate mutagens of N-nitrosoglycosylamines and N-nitroso Amadori compounds, a little explored class of N-nitroso compounds which may be formed in vivo.
PubMed, 1987
Children's pacifiers and baby-bottle nipples from various countries were analysed for their conte... more Children's pacifiers and baby-bottle nipples from various countries were analysed for their content of N-nitrosamines and nitrosatable amines. Using a method involving extraction with artificial saliva, several nitrosamines including N-nitrosodi-n-butylamine (NDBA), N-nitrosodiethylamine (NDEA), N-nitrosodimethylamine (NDMA) and N-nitrosomorpholine (NMOR) were detected in addition to the three nitrosatable amines dibutylamine (DBA), diethylamine (DEA) and dimethylamine (DMA). Upon nitrosation in artificial saliva, these amines produced not only the related N-nitrosamines but also relatively high levels of the corresponding nitramines--N-nitrodibutylamine (NTDBA), N-nitrodiethylamine (NTDEA) and N-nitrodimethylamine (NTDMA). Thus, both N-nitramines and N-nitrosamines should be measured after nitrosation; otherwise, the method probably underestimates 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, are formed in the saliva of babies exposed to these products remains to be confirmed.
PubMed, 1984
A new type of sulfur-containing N-nitrosamino acid, N-nitrosothiazolidine 4-carboxylic acid (NTCA... more A new type of sulfur-containing N-nitrosamino acid, N-nitrosothiazolidine 4-carboxylic acid (NTCA) and N-nitroso 2-methylthiazolidine 4-carboxylic acid (NMTCA), was isolated and identified in the urine of human subjects. Identification was based on identical chromatographic and mass spectral data for the purified urine sample and the synthesized authentic compounds. The amounts of NTCA and NMTCA excreted in 24-h urines of 15 volunteers varied from 0.9 to 35.9 micrograms/day and from 0.4 to 19.8 micrograms/day, respectively. These amounts were 2.4 and 1.6 times greater than that of N-nitrosoproline (NPRO) detected in the same urine samples. Thiazolidine 4-carboxylic acid and its 2-methyl derivative were found to be nitrosated in vitro about 250-500 and 60-300 times more rapidly than proline, respectively. In addition, NTCA and NMTCA were also readily formed by reaction of a mixture of nitrite and L-cysteine, with formaldehyde and acetaldehyde, respectively. Although their origin in human urine is unknown, preliminary results in one human volunteer have shown that some of these compounds are formed endogenously. Thus, measurement of these new sulfur-containing N-nitrosamino acids in the urine may (i) provide another index for endogenous nitrosation reactions in the human body and (ii) allow monitoring of exposure of humans to precursors such as aldehydes and nitrate/nitrite.
Journal of Antimicrobial Agents, 2017
Toxicology and Applied Pharmacology, Dec 1, 1978
PubMed, 1997
Biomarkers of internal dose measure the level of a carcinogen or one of its metabolites in a tiss... more Biomarkers of internal dose measure the level of a carcinogen or one of its metabolites in a tissue or a body fluid such as urine or blood. The choice of a biomarker of internal dose for a particular epidemiological study or type of study requires careful consideration of the period of exposure to which the biomarker relates, host factors related to carcinogen metabolism, invasiveness of sampling, reliability and cost of the biomarker. Before a new biomarker is adopted, it is important to assess these characteristics in transitional studies to ensure that the biomarker will be applied appropriately. Biomarkers of internal dose have been applied most successfully in ecological studies and nested case-control studies, and are especially useful when they provide information about long-term carcinogen exposure.
Journal - Association of Official Analytical Chemists, Sep 1, 1980
A sample of aflatoxin M1-contaminated lyophilized cow's milk was analyzed by 80 laborator... more 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.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 1998
Hemoglobin (Hb) adducts of 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB), a metabolite of two tobacco-... more Hemoglobin (Hb) adducts of 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB), a metabolite of two tobacco-specific nitrosamines [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and N'-nitrosonornicotine], were measured as biomarkers of exposure to tobacco smoke as part of a study on genetic alterations and susceptibility to lung cancer among nonsmokers. HPB-Hb adducts were measured after collection of RBCs by Ficoll gradient in six collaborating centers, release of HPB by alkaline hydrolysis from Hb, clean-up by solid-phase extraction, and analysis of an electron-capturing derivative by gas chromatography-electron capture mass spectrometry. Prior to analysis of samples from study subjects, the reproducibility of this approach was validated in blood from donors. The coefficient of variation of reproducibility of paired aliquots from five samples ranged from 7 to 25%; the within-sample reproducibilities of four and eight aliquots were 4 and 16%, respectively. The study subjects consisted of...
European Journal of Pharmacology, 1990
underly its capability to ameliorate outcome in different experimental models of cerebral ischemi... more underly its capability to ameliorate outcome in different experimental models of cerebral ischemia as well as in patients affected b) cerebrovascular insufficiency (3). Re[erences
IARC monographs on the evaluation of carcinogenic risks to humans / World Health Organization, International Agency for Research on Cancer, 2006
Mutation Research: Fundamental And Molecular Mechanisms Of Mutagenesis, Jun 1, 1985
Mutation research, Jun 1, 1982
![Research paper thumbnail of Gas Chromatography. Mass Spectrometry Analysis of 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]Pyridine in Urine and Feces](https://attachments.academia-assets.com/115457071/thumbnails/1.jpg)
](Environmental Health Perspectives, Mar 1, 1993
A method has been developed to measure levels of2-amino-1-methyl-6phenylimidazo[4,5-blpyridine (P... more A method has been developed to measure levels of2-amino-1-methyl-6phenylimidazo[4,5-blpyridine (PhIP) excreted in urine and feces. The method involves organic solvent extraction, derivatization to form electron-capturing bispentafluorobenzyl derivatives, and analysis by gas chromatography-negative ion chemical ionization mass spectrometry using a deuteriumnlabeled internal standard. The method can detect PhIP at levels ofless than 1 ng/g in rat urine (5 ng/24 hr) and 5 ng/g (wet weight) in rat feces (50 ng/24 hr). Sprague-Dawley rats given a single 50 Ag dose of PhIP by gavage excreted an average of 0.6% of the dose in the urine and 25% ofthe dose in the feces as unchanged PhIP, in the first 4 days after treatment. To make this method applicable for the analyses of biological fluids of PhIP-exposed human subjects, it is now being improved by using immunoaffinity chromatography.
Journal of Cancer Research and Clinical Oncology, Jul 1, 1984
To quantitate endogenous nitrosation reactions in man, the quantity of N-nitrosoproline (NPRO) ex... more To quantitate endogenous nitrosation reactions in man, the quantity of N-nitrosoproline (NPRO) excreted in the urine after ingestion of proline and/or nitrate was estimated. When this monitoring method (NPRO test) was applied in clinical and field studies, several hitherto unidentified N-nitroso compounds were frequently detected. These were recently identified as sulphur-containing N-nitrosamino acids, N-nitrosothiazolidine 4-carboxylic acid (NTCA), and trans- and cis-isomers of N-nitroso-2-methylthiazolidine 4-carboxylic acid (NMTCA). NTCA and NMTCA were readily formed in vitro following nitrosation at acidic pH of the respective precursor, thiazolidine 4-carboxylic acid (TCA) or of 2-methylthiazolidine 4-carboxylic acid (MTCA). As the latter compounds can be formed by reaction of L-cysteine with formaldehyde or acetaldehyde, respectively, NTCA and NMTCA were also formed by reacting L-cysteine with the respective aldehyde and with nitrite at optimal pH (2.5 for NTCA and 4.5 for NMTCA). Up to 95% of NTCA and NMTCA given orally to fasted rats was recovered as such in urine and faeces within 2 days. Administration of TCA or MTCA, together with nitrite increased the urinary excretion of NTCA and NMTCA, as did co-administration of L-cysteine, nitrite, and the respective aldehyde. NTCA and NMTCA were also detected in the 24-h urine of human volunteers, and smokers tended to excrete higher levels than nonsmokers. Daily excretion levels varied, however, and a diet supplemented with ascorbic acid significantly decreased the total amount of nitrosamino acids. NTCA and NMTCA may occur in human urine as a result of (i) intake of preformed N-nitroso compounds; (ii) intake of thiazolidine 4-carboxylic acid or its 2-methyl derivative and subsequent nitrosation in vivo; (iii) endogenous two-step synthesis by the reaction of L-cysteine with the respective aldehyde and a nitrosating agent. Thus, measurement of NTCA and NMTCA together with NPRO in urine may provide an index for the exposure of human subjects to nitrosamines or their precursors, i.e., nitrosating agents, certain aldehydes, or aldehyde-generating compounds. Our data demonstrate unequivocally that N-nitroso compounds are formed in the human body, as suggested previously by Druckrey. Their relevance to human cancer at specific sites should now be investigated.
Supplementary Figure from Bioavailability of Sulforaphane from Two Broccoli Sprout Beverages: Res... more Supplementary Figure from Bioavailability of Sulforaphane from Two Broccoli Sprout Beverages: Results of a Short-term, Cross-over Clinical Trial in Qidong, China
Chemical Research in Toxicology, Aug 8, 2001
Carcinogenesis, 1982
Samples of opium pipe scrapings (opium dross, called sukhteh locally), but not of crude opium, co... more Samples of opium pipe scrapings (opium dross, called sukhteh locally), but not of crude opium, collected in an area with a high incidence of oesophageal cancer in north-east Iran, were shown to contain pro-mutagens, producing mostly frameshift mutations in Salmonella typhimurium strains TA1538 and TA98 after metabolic activation. Pyrolysis of opium and of its major alkaloid, morphine, yielded smoke condensates with mutagenic activities 10 and 100 times higher, respectively, than that of the sukhteh samples tested. Heterocyclic aromatic hydrocarbons and primary aromatic amines present at different concentrations in these three pyrolysates are considered to be the major active principles. Opium addiction has been implicated as a risk factor in bladder cancer in humans and the ingestion of opium pyrolysates, in conjunction with dietary deficiencies, may be related to the high incidence of oesophageal cancer in north-east Iran, although causality has not been established.
Investigative Ophthalmology & Visual Science, Dec 1, 2002
PubMed, 1987
A series of nine glycosylamines and an Amadori compound and their N-nitroso derivatives were synt... more A series of nine glycosylamines and an Amadori compound and their N-nitroso derivatives were synthesized. The structures were ascertained by spectroscopy and elemental analysis. The N-nitroso compounds were further characterized by denitrosation with hydrogen bromide-acetic acid, followed by detection of the liberated NO by a chemiluminescence detector. N-Nitroso derivatives of N-p-nitrophenyl/p-methylphenyl/p-carboxyphenyl pentosylamines, N-p-methylphenyl-1-deoxy-D-fructosylamine (Amadori compound) and N-3-ethylindole-D-xylosylamine were shown to be directly-acting mutagens in Salmonella typhimurium TA100. The activity of some of the compounds was similar to that of N-ethyl-N-nitrosourea. Their mutagenic activity was shown to be dependent on the structure of the amine and the sugar moieties and requires the presence of free hydroxyl groups in the sugar. The mutagenicity of N-nitrosoglycosylamines was attributed to their hydrolysis to arene diazonium cations. Their formation was detected via azo-coupling with N-ethyl-1-naphthylamine, using spectrophotometric and mass-spectrometric analyses. Our data implicate arene (alkyl) diazonium cations as the ultimate mutagens of N-nitrosoglycosylamines and N-nitroso Amadori compounds, a little explored class of N-nitroso compounds which may be formed in vivo.
PubMed, 1987
Children's pacifiers and baby-bottle nipples from various countries were analysed for their conte... more Children's pacifiers and baby-bottle nipples from various countries were analysed for their content of N-nitrosamines and nitrosatable amines. Using a method involving extraction with artificial saliva, several nitrosamines including N-nitrosodi-n-butylamine (NDBA), N-nitrosodiethylamine (NDEA), N-nitrosodimethylamine (NDMA) and N-nitrosomorpholine (NMOR) were detected in addition to the three nitrosatable amines dibutylamine (DBA), diethylamine (DEA) and dimethylamine (DMA). Upon nitrosation in artificial saliva, these amines produced not only the related N-nitrosamines but also relatively high levels of the corresponding nitramines--N-nitrodibutylamine (NTDBA), N-nitrodiethylamine (NTDEA) and N-nitrodimethylamine (NTDMA). Thus, both N-nitramines and N-nitrosamines should be measured after nitrosation; otherwise, the method probably underestimates 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, are formed in the saliva of babies exposed to these products remains to be confirmed.
PubMed, 1984
A new type of sulfur-containing N-nitrosamino acid, N-nitrosothiazolidine 4-carboxylic acid (NTCA... more A new type of sulfur-containing N-nitrosamino acid, N-nitrosothiazolidine 4-carboxylic acid (NTCA) and N-nitroso 2-methylthiazolidine 4-carboxylic acid (NMTCA), was isolated and identified in the urine of human subjects. Identification was based on identical chromatographic and mass spectral data for the purified urine sample and the synthesized authentic compounds. The amounts of NTCA and NMTCA excreted in 24-h urines of 15 volunteers varied from 0.9 to 35.9 micrograms/day and from 0.4 to 19.8 micrograms/day, respectively. These amounts were 2.4 and 1.6 times greater than that of N-nitrosoproline (NPRO) detected in the same urine samples. Thiazolidine 4-carboxylic acid and its 2-methyl derivative were found to be nitrosated in vitro about 250-500 and 60-300 times more rapidly than proline, respectively. In addition, NTCA and NMTCA were also readily formed by reaction of a mixture of nitrite and L-cysteine, with formaldehyde and acetaldehyde, respectively. Although their origin in human urine is unknown, preliminary results in one human volunteer have shown that some of these compounds are formed endogenously. Thus, measurement of these new sulfur-containing N-nitrosamino acids in the urine may (i) provide another index for endogenous nitrosation reactions in the human body and (ii) allow monitoring of exposure of humans to precursors such as aldehydes and nitrate/nitrite.
Journal of Antimicrobial Agents, 2017
Toxicology and Applied Pharmacology, Dec 1, 1978
PubMed, 1997
Biomarkers of internal dose measure the level of a carcinogen or one of its metabolites in a tiss... more Biomarkers of internal dose measure the level of a carcinogen or one of its metabolites in a tissue or a body fluid such as urine or blood. The choice of a biomarker of internal dose for a particular epidemiological study or type of study requires careful consideration of the period of exposure to which the biomarker relates, host factors related to carcinogen metabolism, invasiveness of sampling, reliability and cost of the biomarker. Before a new biomarker is adopted, it is important to assess these characteristics in transitional studies to ensure that the biomarker will be applied appropriately. Biomarkers of internal dose have been applied most successfully in ecological studies and nested case-control studies, and are especially useful when they provide information about long-term carcinogen exposure.
Journal - Association of Official Analytical Chemists, Sep 1, 1980
A sample of aflatoxin M1-contaminated lyophilized cow's milk was analyzed by 80 laborator... more 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.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 1998
Hemoglobin (Hb) adducts of 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB), a metabolite of two tobacco-... more Hemoglobin (Hb) adducts of 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB), a metabolite of two tobacco-specific nitrosamines [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and N'-nitrosonornicotine], were measured as biomarkers of exposure to tobacco smoke as part of a study on genetic alterations and susceptibility to lung cancer among nonsmokers. HPB-Hb adducts were measured after collection of RBCs by Ficoll gradient in six collaborating centers, release of HPB by alkaline hydrolysis from Hb, clean-up by solid-phase extraction, and analysis of an electron-capturing derivative by gas chromatography-electron capture mass spectrometry. Prior to analysis of samples from study subjects, the reproducibility of this approach was validated in blood from donors. The coefficient of variation of reproducibility of paired aliquots from five samples ranged from 7 to 25%; the within-sample reproducibilities of four and eight aliquots were 4 and 16%, respectively. The study subjects consisted of...
European Journal of Pharmacology, 1990
underly its capability to ameliorate outcome in different experimental models of cerebral ischemi... more underly its capability to ameliorate outcome in different experimental models of cerebral ischemia as well as in patients affected b) cerebrovascular insufficiency (3). Re[erences
IARC monographs on the evaluation of carcinogenic risks to humans / World Health Organization, International Agency for Research on Cancer, 2006
Mutation Research: Fundamental And Molecular Mechanisms Of Mutagenesis, Jun 1, 1985
Mutation research, Jun 1, 1982
Environmental Health Perspectives, Mar 1, 1993
A method has been developed to measure levels of2-amino-1-methyl-6phenylimidazo[4,5-blpyridine (P... more A method has been developed to measure levels of2-amino-1-methyl-6phenylimidazo[4,5-blpyridine (PhIP) excreted in urine and feces. The method involves organic solvent extraction, derivatization to form electron-capturing bispentafluorobenzyl derivatives, and analysis by gas chromatography-negative ion chemical ionization mass spectrometry using a deuteriumnlabeled internal standard. The method can detect PhIP at levels ofless than 1 ng/g in rat urine (5 ng/24 hr) and 5 ng/g (wet weight) in rat feces (50 ng/24 hr). Sprague-Dawley rats given a single 50 Ag dose of PhIP by gavage excreted an average of 0.6% of the dose in the urine and 25% ofthe dose in the feces as unchanged PhIP, in the first 4 days after treatment. To make this method applicable for the analyses of biological fluids of PhIP-exposed human subjects, it is now being improved by using immunoaffinity chromatography.
Journal of Cancer Research and Clinical Oncology, Jul 1, 1984
To quantitate endogenous nitrosation reactions in man, the quantity of N-nitrosoproline (NPRO) ex... more To quantitate endogenous nitrosation reactions in man, the quantity of N-nitrosoproline (NPRO) excreted in the urine after ingestion of proline and/or nitrate was estimated. When this monitoring method (NPRO test) was applied in clinical and field studies, several hitherto unidentified N-nitroso compounds were frequently detected. These were recently identified as sulphur-containing N-nitrosamino acids, N-nitrosothiazolidine 4-carboxylic acid (NTCA), and trans- and cis-isomers of N-nitroso-2-methylthiazolidine 4-carboxylic acid (NMTCA). NTCA and NMTCA were readily formed in vitro following nitrosation at acidic pH of the respective precursor, thiazolidine 4-carboxylic acid (TCA) or of 2-methylthiazolidine 4-carboxylic acid (MTCA). As the latter compounds can be formed by reaction of L-cysteine with formaldehyde or acetaldehyde, respectively, NTCA and NMTCA were also formed by reacting L-cysteine with the respective aldehyde and with nitrite at optimal pH (2.5 for NTCA and 4.5 for NMTCA). Up to 95% of NTCA and NMTCA given orally to fasted rats was recovered as such in urine and faeces within 2 days. Administration of TCA or MTCA, together with nitrite increased the urinary excretion of NTCA and NMTCA, as did co-administration of L-cysteine, nitrite, and the respective aldehyde. NTCA and NMTCA were also detected in the 24-h urine of human volunteers, and smokers tended to excrete higher levels than nonsmokers. Daily excretion levels varied, however, and a diet supplemented with ascorbic acid significantly decreased the total amount of nitrosamino acids. NTCA and NMTCA may occur in human urine as a result of (i) intake of preformed N-nitroso compounds; (ii) intake of thiazolidine 4-carboxylic acid or its 2-methyl derivative and subsequent nitrosation in vivo; (iii) endogenous two-step synthesis by the reaction of L-cysteine with the respective aldehyde and a nitrosating agent. Thus, measurement of NTCA and NMTCA together with NPRO in urine may provide an index for the exposure of human subjects to nitrosamines or their precursors, i.e., nitrosating agents, certain aldehydes, or aldehyde-generating compounds. Our data demonstrate unequivocally that N-nitroso compounds are formed in the human body, as suggested previously by Druckrey. Their relevance to human cancer at specific sites should now be investigated.
Supplementary Figure from Bioavailability of Sulforaphane from Two Broccoli Sprout Beverages: Res... more Supplementary Figure from Bioavailability of Sulforaphane from Two Broccoli Sprout Beverages: Results of a Short-term, Cross-over Clinical Trial in Qidong, China