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PubMed1982

Structure activity studies with N-nitrosamines using Salmonella typhimurium and Escherichia coli.

Mutagenic activities of a large number of nitrosamines were determined using Salmonella histidine reversion and Escherichia coli arginine reversion assays. The cyclic nitrosamines exhibited a close correlation between their mutagenic and carcinogenic properties, while no such relationship was evident with the aliphatic nitrosamines. Substitution of cyclic nitrosamines with methyl, hydroxy and oxy groups did not alter the mutagenic activities. However, when positions alpha to the N-nitroso groups were substituted with methyl groups, the biological activity was eliminated. Substitution with halogens enhanced, whereas carboxyl substitution eliminated the biological activity. The E. coli assay not only substantiated the observations made with Salmonella, but also demonstrated mutagenic activity in the case of certain carcinogenic nitrosamines which were not mutagenic in the Salmonella assay.

Animals↗
PubMed1978

Diffusion of nitrosamines through protective gloves.

A simple experimental demonstration of the permeability of protective gloves to volatile nitrosamines has been carried out. Rubber and polyvinyl chloride (PVC) gloves were turned inside out and the fingers filled with dilute solutions of nitrosamines in hexane. The outer faces of the fingers were washed with water at various times and the nitrosamine content of these washings determined. From these measurements the proportions of the various nitrosamines passing through the gloves were calculated. For both types of gloves N-nitrosopyrrolidine (NPYR) permeated the fingers most rapidly and to the greatest extent. Only a relatively small amount of N-nitrosodibutylamine (NDBA) was transmitted. It was also established that the rubber gloves themselves did not contain any of the common volatile nitrosamines; N-nitrosomethylphenylamine and N-nitrosodiphenylamine were also absent.

Chromatography, Gas↗
PubMed1981

Analytical methodology for sample preparation, detection, quantitation, and confirmation of N-nitrosamines in foods.

Significant advances have been made over the past decade in methodology for the analysis of foods and other samples for volatile N-nitrosamines. Procedures for the isolation, cleanup, and concentration of N-nitrosamines were developed and applied to a broad range of food types. Several chromatographic techniques and systems have also been developed which are capable of resolving N-nitrosamines in complex mixtures in a single run, and the use of highly selective detectors has decreased sample preparation time while increasing sensitivity and precision. Unequivocal confirmation of N-nitrosamines in foods can now be achieved by mass spectrometry at low to sub-microgram/kg levels. However, further development of methodology for nonvolatile N-nitroso compounds is needed. This review paper discusses these and other topics related to the analysis of foods for N-nitrosamines.

Food Analysis↗
PubMed1982

A rapid and sensitive method for the determination of non-volatile n-nitroso compounds in foods and human urine: recent data concerning volatile N-nitrosamines in dried foods and malt-based beverages.

Methods are described for the rapid screening of various foods for the presence of nitrosamino acids (mainly NPRO and NSAR) and of hydroxylated nitrosamines (mainly BHBN, NHPYR and NDELA). Rapid screening methods (HPLC-TEA and GC-TEA) are also described for the determination of the above mentioned nitrosamines in human urine. Recent monitoring data indicate that, in Canada, the NDMA levels in both malt and beer have decreased significantly during the last two years. Contrary to published reports, no volatile nitrosamines could be detected in vegetable oils or pasteurized milk. A new method, based on oxidation of nitrosamines and nitramines and reanalysis by GC-TEA, is described for the confirmation of low microgram/kg levels of volatile nitrosamines in foods.

Beer↗
PubMed1980

Chemical studies on tobacco smoke LXVIII. Analysis of volatile and tobacco-specific nitrosamines in tobacco products.

The yields of volatile N-nitrosamines in cigarette smoke are primarily dependent upon the nitrate content of the tobacco and, to some extent, on the protein content. Cellulose acetate tips, such as those found on most commercial filter cigarettes, selectively remove at least 70% of the volatile N-nitrosamines, independently of the pH of the weakly acidic or weakly alkaline smoke. So far, three tobacco-specific N-nitrosamines have been detected in tobacco and tobacco smoke. During tobacco processing and smoking, N'-nitrosonornicotine is formed by nitrosation of nicotine and, to a minor degree, by nitrosation of nornicotine, whereas 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone originates from oxidative nitrosation of nicotine. N'-Nitrosoanatabine is formed by nitrosation of the second most abundant tobacco alkaloid, anatabine. The tobacco-specific N-nitrosamines in the smoke arise partly from the tobacco by transfer and partly by nitrosation of the alkaloids during smoking (pyrosynthesis). Preliminary results indicate that cellulose acetate filter tips may selectively remove considerable amounts of the nonvolatile nitrosamines from the smoke.

Chromatography, High Pressure Liquid↗
PubMed2001

Predicting the mutagenicity of tobacco-related N-nitrosamines in humans using 11 strains of Salmonella typhimurium YG7108, each coexpressing a form of human cytochrome P450 along with NADPH-cytochrome P450 reductase.

Tobacco, including snuff and chewing tobacco, contains N-nitrosamines such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-nitrosodiethylamine (NDEA), N-nitrosopyrrolidine (NPYR), N-nitrosopiperidine (NPIP), N-nitrosomorpholine (NMOR), N-nitrosonornicotine (NNN), N-nitrosoanabasine (NABS), and N-nitrosoanatabine (NATB). The role of human cytochrome P450 (CYP) in the metabolic activation of these tobacco-related N-nitrosamines was examined by a Salmonella mutation test using genetically engineered Salmonella typhimurium (S. typhimurium) YG7108 cells each expressing a form of human CYP (CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, or CYP3A5) together with human NADPH-cytochrome P450 reductase. Mutagen production from NNK was catalyzed by CYP in the following order: CYP1A2, CYP1A1, CYP1B1, CYP2A6, CYP2C19, CYP3A4. The metabolic activation of one of the N-alkylnitrosamines, NDEA, was mediated by CYP2A6, followed by CYP2E1. Cyclic N-nitrosamines such as NPYR, NPIP, and NMOR were also primarily activated by CYP2A6, and to a lesser extent by CYP2E1. NNN, a pyridine derivative of NPYR, was activated by CYP1A1 at an efficiency similar to that of CYP2A6. NABS, a pyridine derivative of NPIP, was mainly activated by CYP3A4, followed by CYP1A1 and CYP2A6. Thus, the addition of a pyridine ring to NPYR or NPIP altered the forms of CYP primarily responsible for mutagenic activation. NATB was metabolically activated solely by CYP2A6, whereas the genotoxicity of NATB was much lower than that of NNN or NPYR. Based on these data, we conclude that CYP2A6 was responsible for the mutagenic activation of essentially all tobacco-related N-nitrosamines tested in the present study.

Cytochrome P-450 Enzyme System↗
PubMed1980

[Analysis of volatile nitrosamines in food of animal origin].

A method is described for the fluorescence-spectrophotometric densitometric determination of nitrosamines. For this purpose, foods of animal origin are vacuum-distilled, the distilled-over nitrosamines are extracted with methylene chloride from an acid medium and, after cleavage by hydrogen bromide, the corresponding amines are reacted with 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole. The purificaton of the extract and the resolution of the corresponding fluorescent amine derivatives are effected simultaneously by two-dimensional thin-layer chromatography. The determination is achieved by in situ fluorescence spectrophotometry against test substances on the same slab. This method seems useful for investigations into the formation of nitrosamines in foods of animal origin because it permits to detect nitrosamine concentrations as low as 0.1 microgram/kg of food.

Animals↗
PubMed2006

Processed meat consumption, dietary nitrosamines and stomach cancer risk in a cohort of Swedish women.

Processed meat consumption has been associated with an increased risk of stomach cancer in some epidemiological studies (mainly case-control). Nitrosamines may be responsible for this association, but few studies have directly examined nitrosamine intake in relation to stomach cancer risk. We prospectively investigated the associations between intakes of processed meat, other meats and N-nitrosodimethylamine (the most frequently occurring nitrosamine in foods) with risk of stomach cancer among 61,433 women who were enrolled in the population-based Swedish Mammography Cohort. Information on diet was collected at baseline (between 1987 and 1990) and updated in 1997. During 18 years of follow-up, 156 incident cases of stomach cancer were ascertained. High consumption of processed meat, but not of other meats (i.e., red meat, fish and poultry), was associated with a statistically significant increased risk of stomach cancer. After adjustment for potential confounders, the hazard ratios for the highest compared with the lowest category of intake were 1.66 (95% CI = 1.13-2.45) for all processed meats, 1.55 (95% CI = 1.00-2.41) for bacon or side pork, 1.50 (95% CI = 0.93-2.41) for sausage or hotdogs and 1.48 (95% CI= 0.99-2.22) for ham or salami. Stomach cancer risk was 2-fold higher among women in the top quintile of N-nitrosodimethylamine intake when compared with those in the bottom quintile (hazard ratio = 1.96; 95% CI = 1.08-3.58). Our findings suggest that high consumption of processed meat may increase the risk of stomach cancer. Dietary nitrosamines might be responsible for the positive association.

Adult↗
PubMed1994

Volatile N-nitrosamines and their precursors in Chinese salted fish--a possible etological factor for NPC in china.

Epidemiological studies show that the consumption of Chinese salted fish is a causative factor for nasopharyngeal carcinoma (NPC) in southern China. In the present study, N-nitrosamines and their precursors were analyzed in 145 samples of cooked, salted fish collected from various areas in China. The results show that N-dimethylnitrosamine (NDMA), N-diethylnitrosamine (NDEA), N-nitrosopyrrolidine (NPYR) and N-nitrosopiperidine (NPIP) were present in the salted fish. Total volatile N-nitrosamines (TVN) in the salted fish were 0.028 to 4.54 mg/kg. The samples from areas with higher NPC risk showed a higher average level of TVN than those from areas of lower NPC risk. Positive correlations were found between the levels of NDMA, NDEA and TVN and mortality from NPC. Although neither the nitrates nor the nitrites in the salted fish were present at significantly high levels, in vitro data regarding nitrosation of salted fish showed that the N-nitrosamine content had increased substantially. The results support the conclusion that the high NPC risk in southern Chinese may be attributed to consumption of salted fish containing high levels of N-nitrosamines.

Animals↗
PubMed1981

Alkylation of DNA and tissue specificity in nitrosamine carcinogenesis.

A peculiarity of nitrosamines is the high degree of cell and organ specificity in inducing tumors. There is substantial evidence that the initiation of the carcinogenesis process by carcinogens of this group is linked to the metabolic competence of the target tissue or cell to convert these carcinogens into mutagenic metabolites and to the binding of those metabolites to cellular DNA. Alkylation occurs in the DNA at the N-1, N-3, and N-7 positions of adenine; the N-3, N-7, and O6 of guanine; the N-3, and O2 of cytosine; and the N-3, O4, and O2 of thymine; and the phosphate groups. The initial proportion of each DNA adduct depends upon the alkylating agent used. The various DNA adducts are lost to a variable extent from DNA in vivo by spontaneous release of bases and/or by specific DNA repair processes. Studies conducted in vitro and vivo indicate that alkylation at the oxygen atoms of DNA bases is more critical than alkylation at other positions in the mutagenesis and carcinogenesis induced by N-nitroso compounds. In particular, tissues in which tumors occur more frequently after a pulse dose of nitrosamine are those in which O6-alkylguanine persists longest in DNA, presumably resulting in an increased probability that a miscoding event (mutation) will take place during DNA synthesis. The more rapid removal of O6-methylguanine from the DNA of liver (as compared with extrahepatic tissues) of rats has been associated with the absence of tumor production in this organ by a single dose of dimethylnitrosamine; however, a significant incidence of liver tumors is observed if the same dose is given 24 hr after partial hepatectomy, and tumors are induced by such a dose of dimethylnitrosamine in the liver of hamsters, which has a low capacity to remove O6-methylguanine from its DNA. These data also indicate that the rate of disappearance of 7-methylguanine from the liver or extrahepatic tissues is independent of the dose of dimethylnitrosamine; whereas O6-methylguanine is lost from DNA more rapidly after a low dose of this nitrosamine. It has been shown that in liver the removal of O6-methylguanine but not other DNA adducts, from DNA can be affected by pretreating the animals with N-nitroso compounds. The modulation of DNA repair processes observed after a single dose and after chronic treatment with nitrosamines is discussed in relation to the tissue-specific carcinogenic effect of this group of carcinogens.

Alkylation↗
PubMed1980

The mutagenicity of 45 nitrosamines in the Salmonella typhimurium.

The correlation between mutagenicity in the rat liver microsome--mediated Salmonella Mutagenicity Assay of Ames and carcinogenicity in rats was examined with three groups of nitrosamines. Qualitatively the correlation was good, but there was poor correlation between mutagenic potency and carcinogenic potency. Of 23 cyclic nitrosamines, 19 were carcinogenic and mutagenic, and two were carcinogenic but not mutagenic, and the carcinogenicity studies of the remaining two are not complete. Of six symmetrical aliphatic nitrosamines, five were carcinogenic and mutagenic while only one carcinogen was not mutagenic. The greatest discrepancy occurred among 16 asymmetric nitrosamines, where 11 were both carcinogenic and mutagenic, four were carcinogenic but nonmutagenic, and one carcinogenicity study is incomplete.

Animals↗
PubMed1984

Sources of N-nitrosamine contamination in foods.

It has been well established that human foods may contain trace amounts of carcinogenic N-nitrosamines. Originally, it was thought that the use of nitrite as a curing agent for flesh foods was the major source of these trace compounds in the diet. Subsequent research has clearly shown that other processing and packaging procedures can also introduce trace amounts of these carcinogens into foods. These procedures include drying foods in direct flame heated air, migration from food contact surfaces and direct addition as contaminants. In addition, other reports of N-nitrosamines in foods have less well defined routes of contamination. These sources of N-nitrosamines in foods will each be briefly reviewed in this paper and recent data from our laboratory concerning N-nitrosamines in products which directly contact foods presented. We also are reporting the N-nitrosothiazolidine content of fried-out bacon fat.

Animals↗
PubMed1994

Biomonitoring of hemoglobin adducts: aromatic amines and tobacco-specific nitrosamines.

A new analytical procedure has been developed for the simultaneous determination of human hemoglobin adducts from aromatic amines and tobacco-specific nitrosamines. These tobacco-related hemoglobin adducts were determined in nonsmokers, smokers, and users of nasal snuff. Adducts from aminobiphenyl compounds are good biomarkers of exposure to tobacco smoke; they are not elevated in users of nasal snuff. However, a significant contribution of environmental exposure to aromatic amines and/or the corresponding nitroaromatics makes it difficult to evaluate passive exposure to tobacco smoke. The best biomarkers for exposure to tobacco smoke should in theory be adducts arising from tobacco-specific nitrosamines. The common adduct from N'-nitrosonornicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone releases 4-hydroxy-1-(3-pyridyl)-1-butanone from hemoglobin upon mild alkaline hydrolysis and only marginal differences are found in the adduct level in smokers and nonsmokers. The reason for this observation is not yet understood and is currently under investigation. However, the adduct formed by tobacco-specific nitrosamines is well suited for the detection of oral and nasal tobacco use. Only by simultaneous determination of both adducts formed by aromatic amines and tobacco-specific nitrosamines is it possible to differentiate between nonsmokers, smokers, and nasal snuff users.

Aminobiphenyl Compounds↗
PubMed1984

Mutagenicity of alpha-hydroxy N-nitrosamines in V79 Chinese hamster cells.

Carcinogenic and mutagenic N-nitrosodialkylamines are metabolically activated through alpha-hydroxylation. The synthesis, chemical properties, and microbial mutagenicity of alpha-hydroxy N-nitrosamines have been reported previously. Potent mutagenicity of four N-nitroso-N-(hydroxymethyl)-alkylamines (alkyl = methyl, ethyl, propyl, and butyl) was demonstrated in the present study in V79 Chinese hamster cells, ouabain resistance being used as an indicator. All the compounds were strong mutagens in the absence of metabolic activation systems. The mutagenic and cytotoxic potencies correlated well with each other, and depended on the alkyl group, decreasing in potency in the following order: methyl greater than ethyl greater than propyl = butyl. Their alkylating reactivity was measured by alkylation of thiophenol, and a good linear relationship was observed between the mutagenic and cytotoxic potencies and their alkylating reactivity. The mutagenic and cytotoxic potencies of the alpha-hydroxy N-nitrosamines in V79 cells were well correlated with those of alpha-acetoxy and alpha-hydroperoxy N-nitrosamines with respect to the effect of alkyl group. The results obtained here supported further that alpha-hydroxy N-nitrosamine is the active species in the metabolic activation of N-nitrosodialkylamine.

Alkylating Agents↗
PubMed1983

Interference of acetoxyalkyl-nitrosamines with limb bud differentiation in organ culture.

alpha-acetoxynitrosamines have been used as model compounds to study biological activity of N-nitrosamines. After hydrolytic cleavage they yield an "active intermediate" (the hydroxynitrosamine) which presumably also arises as metabolite of N-nitrosamines. We tested eight N-nitrosamines mono-substituted at the alpha-carbon with an acetoxy group for their teratogenic potential in a mouse limb bud culture system. The following results were obtained: 1. The methyl compound (MOAc-MNA) - a derivative of dimethynitrosamine - proved to be the strongest teratogen in this group of chemicals. 2. The tertiary-butyl derivative - releasing a carbonium ion of low chemical reactivity - possessed the lowest activity in our test system. 3. The primary alpha-acetates with unbranched side chains (POAc-MNA or BOAc-MNA) were more active than the corresponding derivatives with branched side chains. 4. The secondary alpha-acetate (EOAc-ENA) was clearly less active than the primary alpha-acetate (EOAc-MNA). 5. A teratogenic potential could also be demonstrated in the organ culture system with the cyclic derivative: N-nitroso-alpha-acetoxy-pyrrolidine (NAPYR). 6. With the use of limb buds from 12-day-old mouse embryos the explants showed the highest susceptibility to the teratogens on the first day of culture. No effect could be produced if the substances were added to the culture medium at the third day of culture or later. 7. When initiating the culture with limb buds from 11-day-old mouse embryos the concentrations needed to induce typical effects were lower than those tested with 12-day-old explants. 8. Typical and pronounced impairment with morphogenetic differentiation could be induced by MOAc-MNA if the substance was present in the medium for less than 60 min - the shortest period tested was 15 min. 9. A different abnormality pattern could be induced with the various substances tested. This may partly be explained by a quite different stability of the compounds in the test system. 10. N-Nitrosamines must be expected to be highly teratogenic if they can be "activated" in embryonic tissues. Such an activation into potent electrophilic agents does not occur in rodents under normal conditions. It will be interesting to study if such activity can be "induced" in embryonic tissues of rodents or if it is already present in embryonic tissues of primates.

Animals↗
PubMed1989

Cell type specific, receptor-mediated modulation of growth kinetics in human lung cancer cell lines by nicotine and tobacco-related nitrosamines.

The objective of this study was to investigate a potential involvement of nicotinic cholinergic receptors in the mediation of cell type specific biological effects of nicotine and the two tobacco-related nitrosamines N-nitrosodiethylamine (DEN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) on human lung cells. Three well differentiated human lung cancer cell lines that have been reported previously to possess ultrastructural and biochemical features of normal pulmonary neuroendocrine cells, Clara cells and alveolar type II cells, respectively, were used for these experiments. The effects of nicotine, DEN, and NNK on cell proliferation and its modulation by established antagonists of nicotinic and muscarinic cholinergic receptors were studied. In the neuroendocrine cell line, nicotine and the two nitrosamines caused a strong stimulation of cell proliferation that was inhibited by antagonists of nicotinic cholinergic receptors. In the cell lines with features of Clara cells and alveolar type II cells, nicotine did not stimulate cell proliferation. Both nitrosamines stimulated cell proliferation in the cell line with Clara cell features. This effect was not changed by pre-exposure to cholinergic antagonists. The data suggest a selective uptake of nicotine and the two nitrosamines via nicotinic cholinergic receptors in pulmonary neuroendocrine cells.

Adenocarcinoma↗
PubMed1992

In vitro metabolism of bladder carcinogenic nitrosamines by rat liver and urothelial cells.

In order to establish the importance of the target organ in the activation of bladder carcinogens, we compared rat liver and urothelial cell alpha-hydroxylation activities using as substrates N-nitrosobutyl(4-hydroxybutyl)amine and its metabolite N-nitrosobutyl(3-carboxypropyl)amine, two potent urinary bladder carcinogens in animals. Previous studies have shown that the production of molecular nitrogen can serve as an indicator of nitrosamine alpha-hydroxylation. The use of doubly 15N-labelled nitrosamines and the gas chromatography-mass spectrometric detection of 15N2 formed gives a measurement of the extent of this metabolic step. Various amounts of 15N-labelled substrates were incubated for 60 min at 37 degrees C with rat liver S9 preparations or urothelial cell homogenates in the presence of a NADPH generating system. Both enzyme sources metabolized 15N-labelled N-nitrosobutyl(4-hydroxybutyl)amine and N-nitrosobutyl(3-carboxypropyl)amine through the alpha-hydroxylation pathway. Using hepatic S9 fractions, 15N2 production from 15N-labelled N-nitrosobutyl(4-hydroxybutyl)amine increased from 1.69 +/- 0.02 nmol/h per mg protein (mean +/- S.E.) to 5.78 +/- 0.5 with substrate concentrations ranging between 0.55 and 5.55 mM. 15N2 produced by urothelial cell homogenates was about 40-50% that of the liver S9. 15N-labelled N-nitrosobutyl(3-carboxypropyl)amine was also metabolized through the alpha-hydroxylation pathway both by hepatic S9 and urothelial cell homogenates, though to a lesser extent. 15N2 production was about 10-times less than from 15N-labelled N-nitrosobutyl(4-hydroxybutyl)amine, but again urothelial cell 15N2 production was about 40-50% that of the liver. Treatment with phenobarbital resulted in a 2.7-fold increase in the 15N2 produced from 15N-labelled N-nitrosobutyl(4-hydroxybutyl)amine by hepatic S9. No effect was observed with urothelial cell homogenates. Acetone treatment had no effect on 15N2 production from 15N-labelled N-nitrosobutyl(4-hydroxybutyl)amine by hepatic S9, but raised 15N2 production by urothelial cell homogenates 1.8 times. Although the liver has a greater capacity than the bladder for activating the 15N-labelled nitrosamines studied, the target organ can metabolize bladder carcinogens, thus increasing the possibility of a local toxic effect. Moreover, the distribution of P-450 isozymes might be different in the bladder and this could affect the metabolism of nitrosamines reportedly formed in the human bladder in some pathological conditions.

Acetone↗
PubMed1992

Neutrophil-mediated nitrosamine formation: role of nitric oxide in rats.

It is well known that chronic inflammation of the colon and rectum is associated with an increased risk of colorectal cancer, but the mechanisms by which inflammation promotes neoplasia remain undefined. The authors propose that inflammatory neutrophils may produce carcinogenic nitrosamines via the L-arginine-dependent formation of nitrogen oxides such as nitric oxide. Therefore, the objectives of the study were to characterize the L-arginine-dependent formation of nitrogen oxides by inflammatory (elicited) neutrophils using conditions that more closely mimic the extravascular (i.e., interstitial) compartment of the gut and to characterize the neutrophil-dependent N-nitrosation of a model amine to yield its nitrosamine derivative. In the absence of any metabolic activation, adherent, inflammatory neutrophils (2 x 10(6) cells) produced 12.8 +/- 1.4 mumol/L of nitrite during a 4-hour incubation period. Omission of L-arginine and/or inhibition of nitric oxide synthase by the addition of 1 mmol/L NG-nitro-L-arginine methyl ester (L-NAME) resulted in 35%-78% inhibition of nitrite production, suggesting that nitrite was derived from nitric oxide. By comparison, neither circulating rat neutrophils nor elicited rat macrophages produced significant amounts of nitrite under the same conditions. Furthermore, elicited neutrophils (2 x 10(6) cells) were capable of N-nitrosating 2,3-diaminonaphthalene to yield its nitrosamine derivative 1-naphtho-2,3-triazole (282 +/- 12 nmol/L) in a time- and cell-dependent pattern similar to that of nitrite production. Addition of a variety of antioxidants (e.g., ascorbic acid, reduced glutathione, alpha-tocopherol analog), 5-aminosalicylic acid, or L-NAME resulted in 80%-85% inhibition of neutrophil-mediated nitrosamine formation. Taken together, these data suggest that inflammatory neutrophils may represent an important metabolic source of endogenous carcinogens during times of active intestinal inflammation.

Aminosalicylic Acids↗