N-nitrosothiazolidine-4-carboxylic Acid Research Articles

Simultaneous determination of heterocyclic aromatic amines and N-nitrosamines in fried bacon cubes and slices using LC-(ESI/APCI)-MS/MS

Bacon manufacturing involves several processing steps including nitrite curing, followed by cooking processes, typically frying. During these processes, harmful processing contaminants such as N-nitrosamines (NAs) and heterocyclic aromatic amines (HAAs) can be formed. Consequently, we developed and validated a multi-class method for quantification of the most frequently reported HAAs and NAs in fried bacon. Satisfactory repeatability and reproducibility with limits of quantification between 0.1 and 0.5 ng g−1 for most of the compounds were achieved. Quantification in pan-fried bacon cubes and slices revealed generally low levels of individual HAAs (≤1.5 ng g−1), except in ready-to-eat bacon (0.9–2.9 ng g−1). Differences in amounts of individual HAAs were observed in cubes and slices, most likely due to meat thickness. Among volatile NAs (VNAs), only N-nitrosopiperidine (NPIP), N-nitrosopyrolidine (NPYR), and N-nitrosodibutylamine (NDBA) were found at generally low concentrations (≤5 ng g−1). In contrast, non-volatile NAs (NVNAs) were present in all tested samples at considerably higher amounts, for example, N-nitroso-thiazolidine-4-carboxylic acid (NTCA) at 12–77 ng g−1. N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosodipropylamine (NDPA) were not detected in any samples. Statistical evaluation and principal component analysis revealed some differences among tested samples. Dietary exposure estimation of the Danish population to HAAs and NAs showed the highest exposure in the teenage group (10–17 years).

The occurrence of volatile and non-volatile N‐nitrosamines in cured meat products from the Danish market

Several epidemiological studies emphasize the consumption of processed meat products as a risk factor of colorectal cancer, linking N-nitrosamines (NAs) formed during nitrite curing to this cancer risk. The occurrence of volatile N-nitrosamines (VNAs) has over the years been intensively studied while the knowledge on the occurrence and toxicity of non-volatile N-nitrosamines (NVNAs) is still limited. Therefore, this study focuses on quantification of both VNAs and NVNAs in a large selection of processed meat products. For this purpose, a robust, specific and sensitive method allowing analysis of seven VNAs and two NVNAs was optimized and validated using kassler, sausage, and salami. The limit of quantification achieved was 0.1–0.5 ng·g−1 for most of the VNA, and 2.3–4.2 ng·g−1 for the NVNA. In one hundred commercial samples N-nitroso-thiazolidine-4-carboxylic acid (NTCA) was the most frequently detected (97 samples) among all target NAs and it was found at concentrations ranging from 3.1 ng·g−1 to 1660 ng·g−1. The samples contained relatively low mean levels of the individual VNAs (≤1 ng·g−1). The levels of N-nitrosodimethylamine (NDMA), N-nitrosopyrrolidine (NPYR), and N-nitrosopiperidine (NPIP) ranged from non-detectable to 3.8, 10.8 and 2.9 ng·g−1, respectively. A correlation between the detected residual levels of nitrite and/or nitrate and concentrations of individual NAs could not be demonstrated. Based on principle component analysis (PCA) some correlations between salami, sausage and bacon and NAs could be shown.

Analysis of Nitrosamines in Processed Meat Products in Medan City by Liquid Chromatography-Mass Spectrometry.

BACKGROUND:Nitrosamine is a carcinogen and the maximum level in processed meat products set by WHO.AIM:The purpose of this study was to determine nitrosamine levels in meat products in Medan City and compared nitrosamine levels with standards set by WHO.METHODS:The samples analysed were obtained from Berastagi Supermarket, sausages, burgers, corned beef and smoked beef. Nitrosamine levels were determined by reverse phase liquid chromatography-mass spectrometry.RESULTS:The results showed that only 5 out of 20 samples of N-nitroso-thiazolidine-4-carboxylic acid (NTCA) nitrosamine ranged from 501.290 to 4227.492 µg/kg. The highest level of NTCA was found in smoked beef (Chiefs), which is 4227.492 µg/kg. N-nitroso-2-methyl-thiazolidine-4-carboxylic acid (NMTCA) was contained in all the samples analysed which ranged from 20.50 to 989.175 µg/kg. The highest NMTCA nitrosamine content was found in smoked beef (Chiefs), which is 989.175 µg/kg.CONCLUSION:From this study reveal that nitrosamines in meat products exceed the maximum standards set by WHO (10 µg/kg).

Conducting Molecularly Imprinted Polymer (MIP) Chemical Sensors for Toxic N-Nitrosamines Selective Determination in Heat Processed Food of Animal Origin

High-temperature processing of meat food generates in it toxic heteroaromatic amines and nitrosamines (NAs)1,2 causing chronic diseases including hormonal dysfunctions and cancer.3 Therefore, we devised and fabricated chemical sensors for selective determination of the N-nitroso-L-proline (Pro-NO)4 and N-nitroso-thiazolidine-4-carboxylic acid (NT4A) toxins in this food. We applied films of conducting polymers molecularly imprinted (MIPs) with either the Pro-NO or NT4A template as recognition units of these chemosensors. For selection of most appropriate functional monomers, we used DFT at the B3LYP/3-21G(*) level modeling to find phenolic derivative of bis(bithiophene) and a thiosalenCo(III) complex (CS)5,6 suitable to form pre-polymerization complexes with Pro-NO and NT4A, respectively, at the 1:2 template/monomer stoichiometry. The calculated Gibbs free energy gain due to formation of these complexes with a series of NAs was proportional to the UV-vis spectroscopy determined stability constants of these complexes. These constants were relatively high equalling 3.14×109 M-2 and 2.72×1010 M-2for Pro-NO and NT4A, respectively. Then, we electrochemically polymerized these complexes under potentiodynamic conditions. This electropolymerization resulted in depositing thin MIP films on different electrode substrates. After subsequent extraction of the Pro-NO and NT4A templates from MIPs, we used the resulting MIPs with empty imprinted cavities for determination of Pro-NO and NT4A analytes in grilled pork neck samples. We confirmed the presence and then absence of NA templates in the MIP films before and after extraction, respectively, with FTIR spectroscopy and XPS, and then characterized morphology of the films with AFM. For analytical signal transduction, we used piezoelectric microgravimetry (PM) at the Au-QCR/MIP electrodes of EQCM as well as DPV and EIS at the Pt/MIP electrodes. Limits of detection of the chemosensors were 36.9 nM Pro-NO (with EIS) and 46 nM NT4A (with DPV). The chemosensors selectively responded to the target toxins in the presence of interfering compounds of similar composition and structure. Successful selective determination of Pro-NO and NT4A in the food extract samples indicates that the chemosensors are promising as tools for determination of these toxins in food of animal origin.

Urinary levels of N-nitroso compounds in relation to risk of gastric cancer: findings from the shanghai cohort study.

Background N-Nitroso compounds are thought to play a significant role in the development of gastric cancer. Epidemiological data, however, are sparse in examining the associations between biomarkers of exposure to N-nitroso compounds and the risk of gastric cancer.MethodsA nested case-control study within a prospective cohort of 18,244 middle-aged and older men in Shanghai, China, was conducted to examine the association between urinary level of N-nitroso compounds and risk of gastric cancer. Information on demographics, usual dietary intake, and use of alcohol and tobacco was collected through in-person interviews at enrollment. Urinary levels of nitrate, nitrite, N-nitroso-2-methylthiazolidine-4-carboxylic acid (NMTCA), N-nitrosoproline (NPRO), N-nitrososarcosine (NSAR), N-nitrosothiazolidine-4-carboxylic acid (NTCA), as well as serum H. pylori antibodies were quantified in 191 gastric cancer cases and 569 individually matched controls. Logistic regression method was used to assess the association between urinary levels of N-nitroso compounds and risk of gastric cancer.ResultsCompared with controls, gastric cancer patients had overall comparable levels of urinary nitrate, nitrite, and N-nitroso compounds. Among individuals seronegative for antibodies to H. pylori, elevated levels of urinary nitrate were associated with increased risk of gastric cancer. The multivariate-adjusted odds ratios for the second and third tertiles of nitrate were 3.27 (95% confidence interval = 0.76–14.04) and 4.82 (95% confidence interval = 1.05–22.17), respectively, compared with the lowest tertile (P for trend = 0.042). There was no statistically significant association between urinary levels of nitrite or N-nitroso compounds and risk of gastric cancer. Urinary NMTCA level was significantly associated with consumption of alcohol and preserved meat and fish food items.ConclusionThe present study demonstrates that exposure to nitrate, a precursor of N-nitroso compounds, may increase the risk of gastric cancer among individuals without a history of H. pylori infection.

Formation and mitigation of N-nitrosamines in nitrite preserved cooked sausages

Literature on formation and mitigation of N-nitrosamine (NA) and especially non-volatile NA (NVNA) in meat products is scarce and the present study is therefore a relevant contribution to the field. We found positive correlation between the levels of N-nitrosopiperidine (NPIP), N-nitrosohydroxyproline (NHPRO), N-nitrosoproline (NPRO), N-nitrosothiazolidine-4-carboxylic acid (NTCA) and N-nitroso-2-methyl-thiazolidine-4-carboxylic acid (NMTCA) and the amount of nitrite added to cooked pork sausages. The levels studied were 0, 60, 100, 150, 250 and 350mgkg−1. The levels of N-nitrosodimethylamine (NDMA) and N-nitrosopyrrolidine (NPYR) remained at or below limit of quantification. Erythorbic acid inhibited the formation of NHPRO, NPRO, NPIP and NTCA. This inhibition was for NTCA and NMTCA counteracted by addition of free iron. Ascorbyl palmitate had less inhibitory effect than erythorbic acid and a combination of the two provided no further protection. Increasing the black pepper content increased the levels of NPIP and NMTCA. Only slight effects of increased fat content and addition of tripolyphosphate were observed.

Occurrence of volatile and non-volatile N-nitrosamines in processed meat products and the role of heat treatment

Most of the available data on the occurrence of N-nitrosamines (NA) in processed meat products have been generated in the 1980s and 1990s and especially data on the occurrence of non-volatile NA (NVNA) are scarce. Therefore we have studied the levels of volatile nitrosamines (VNA) and NVNA in processed meat products on the Danish market (N = 70) and for comparison also products on the Belgian market (N = 20). The effect of heat treatment on the NA levels, in selected samples, was also studied, in order to enable an evaluation of how preparation before consumption affects the levels of NA. For the Danish products the mean levels of the VNA were generally low (≤0.8 μg kg−1), whereas the mean levels of the NVNA were considerably higher (≤118 μg kg−1). Slightly higher mean levels were indicated for the Belgian products (i.e. VNA ≤1.5 μg kg−1 and NVNA ≤270 μg kg−1). The sums of VNA were higher than 10 μg kg−1 for one Danish sample and two Belgian samples. Levels of up to 2000 and 4000 μg kg−1 of N-nitroso-thiazolidine-4-carboxylic acid (NTCA) an NVNA occurred in the Danish and the Belgian samples, respectively. The majority of the Danish processed meat products contain NVNA but also VNA occur. The levels of NA are comparable with those reported in previous and recent studies; however the frequency in which they are found may be lower and thereby also the mean contents. The levels of N-nitrosopiperidine (NPIP) increased by frying and baking, whereas varying impacts were observed for N-nitrosoproline (NPRO), N-nitrosodimethylamine (NDMA), N-nitrosopyrrolidine (NPYR), N-nitrosodiethylamine (NDEA) and N-nitrosomethylaniline (NMA) depending on the type of product and/or the heat treatment. The levels of the NVNA, NTCA and N-nitroso-2-methyl-thiazolidine 4-carboxylic acid (NMTCA) decreased after frying and baking.

Simultaneous determination of volatile and non-volatile nitrosamines in processed meat products by liquid chromatography tandem mass spectrometry using atmospheric pressure chemical ionisation and electrospray ionisation

A sensitive, selective and generic method has been developed for the simultaneous determination of the contents (μgkg−1 range) of both volatile nitrosamines (VNA) and non-volatile nitrosamines (NVNA) in processed meat products. The extraction procedure only requires basic laboratory equipment and a small volume of organic solvent. Separation and quantification were performed by the developed LC–(APCI/ESI)MS/MS method. The method was validated using spiked samples of three different processed meat products. Satisfactory recoveries (50–130%) and precisions (2–23%) were obtained for eight VNA and six NVNAs with LODs generally between 0.2 and 1μgkg−1, though for a few analyte/matrix combinations higher LODs were obtained (3 to 18μgkg−1). The validation results show that results obtained for one meat product is not always valid for other meat products. We were not able to obtain satisfactory results for N-nitrosohydroxyproline (NHPRO), N-nitrosodibenzylamine (NDBzA) and N-nitrosodiphenylamine (NDPhA). Application of the APCI interface improved the sensitivity of the method, because of less matrix interference, and gave the method a wider scope, as some NAs were ionisable only by APCI. However, it was only possible to ionize N-nitroso-thiazolidine-4-carboxylic acid (NTCA) and N-nitroso-2-methyl-thiazolidine-4-carboxylic acid (NMTCA) by ESI. The validated method was applied for the analysis of processed meat products and contents of N-nitrosodimethylamine (NDMA), N-nitrosopyrrolidine (NPYR), N-nitrosomethylaniline (NMA), N-nitrosoproline (NPRO), NTCA, and NMTCA were found in one or several nitrite cured meat products, whereas none were detected in non-nitrite cured bacon.

N‐Nitrosothiazolidine and its 4‐Carboxylic Acid in Frankfurters Containing Alaska Pollock

ABSTRACTIn marine fish of the gadoid family trimethylamine oxide can decompose to formaldehyde. It can then react with cysteine and cysteamine, that may in turn react with nitrite, if present, to form N‐nitrosothia‐zolidine‐4‐carboxylic acid (NTHZC) and N‐nitrosothiazolidine (NTHZ). The NTHZC and NTHZ content of Alaska pollock surimi‐meat frankfurters were similar to or lower than those found in an all‐meat control, even at 50% substitution. No correlation was found between age of the fish protein prior to processing into surimi meat frankfurters and any measured variables.

Quantitative relationship between oral nitrate-reducing activity and the endogenous formation of N-nitrosoamino acids in humans

Salivary nitrate and nitrite concentrations, in vitro kinetics of nitrate reduction in saliva, and numbers of salivary nitrate-reducing micro-organisms were each compared with N-nitrosoamino acid excretion in 16 humans eating controlled diets. N-Nitrosoproline (NPRO) and N-nitrosothiazolidine-4-carboxylic acid (NTCA) excretion were measured after intake of nitrate (5.24 mmol) and l-proline (4.35 mmol) before and after treatment with an oral antiseptic (Peridex, 0.12% chlorhexidine gluconate). Peridex treatment resulted in a 94% reduction in the numbers of salivary nitrate-reducing bacteria, a decline from 17 to 4% in the amount of salivary nitrate that was reduced to nitrite in vivo, and an 85% reduction in the rate of in vitro nitrate reduction by saliva. Concurrently, there were 62 and 74% inhibitions of endogenous NPRO and NTCA formation, respectively. Correlations of the numbers of nitrate reductase micro-organisms, in vivo oral nitrate reduction and salivary nitrite concentrations, with individual NPRO excretion, indicated that individuals with higher oral nitrate-reducing capacities formed more N-nitrosoamino acid endogenously. These data suggest that individual differences in oral nitrate reduction are a significant factor in gastric nitrosation and account for a large proportion of the interindividual variability in nitrosoamino acid excretion.

Mutagenicity and cytotoxicity ofN‐nitrosothiazolidine‐4‐carboxylic acid

N-Nitrosothiazolidine-4-carboxylic acid (NTCA) was prepared by treating L-thioproline with sodium nitrite at pH 2, 37 degrees C. The compound was characterized by mass spectrometry, infrared spectroscopy and 1H-nuclear magnetic resonance spectroscopy. The cytotoxic and mutagenic properties of NTCA were explored by exposing the human cell line HeLa S3 at 37 degrees C to various concentrations (10 microM-10 mM) of the compound for various periods of time (1-36 h) and by monitoring its effects on cell viability, cell growth, intracellular metabolic activities such as DNA, RNA, and protein synthesis and on DNA repair synthesis ('unscheduled' DNA synthesis). NTCA did not affect the cells' viability at any concentration or incubation period but decreased cell growth at the limiting concentration of 10 mM in the growth medium. NTCA had no effect on RNA and protein synthesis, and, similarly, it had no effect on DNA synthesis at concentrations up to 3 mM. Curiously, the stimulation of DNA synthesis by NTCA was seen at 10 mM after 24 h of incubation. NTCA did not initiate 'unscheduled' DNA synthesis (DNA repair). It is concluded that the compound displays very little cytotoxicity and no mutagenicity in the HeLa S3 test system; hence, its presence in humans and in the human food supply is likely to be of little importance as far as its oncogenic properties are concerned.

Detection of a new nitrosamine, N-nitroso-N-methylaniline, and other nitrosamines in Icelandic smoked mutton

Varying levels (1-48 ppb) of N-nitrosodimethylamine (NDMA), N-nitrosopyrrolidine (NPYR), and a previously undetected nitrosamine, N-nitroso-N-methylaniline (NMA), were detected in Icelandic smoked mutton. Traces (0.6-2.4 ppb) of N-nitrosothiazolidine (NThZ) and low levels (56-475 ppb) of N-nitrosothiazolidine-4-carboxylic acid (NTCA), the two N-nitroso compounds commonly detected in smoked meats, were also present in such products. Evidence presented suggests that NMA in the meat is produced by the interaction of nitrite and smoke generated by burning sheep dung, the traditional source of fuel used for smoking such products. Nitrosation of laboratory-generated sheep dung smoke produced NMA, as well as NDMA and NPYR. The identity of NDMA, NPYR, and NMA was confirmed by mass spectrometry. It is suggested that the formation of all of the above nitrosamines in Icelandic smoked mutton can be minimized by changing or modifying the method of smoking.

Urinary excretion of N-nitrosamino acids and nitrate by inhabitants of high- and low-risk areas for stomach cancer in Poland.

Urine samples were collected from 96 inhabitants of a high-risk rural area and a low-risk urban area for stomach cancer in Poland, according to the following protocol: (1) when they were undosed; (2) after ingestion of proline 3 times a day; and (3) after ingestion of proline together with vitamin C 3 times a day. The samples were analyzed for N-nitrosamino acids and nitrates, as indices of exposure to preformed and endogenously formed N-nitrosamines. The median values of N-nitrosoproline (NPRO) and N-nitrosothiazolidine 4-carboxylic acid (NTCA) excreted in the urine of undosed subjects were not different between the two areas; but N-nitrososarcosine and 3-(N-nitroso-N-methylamino)propionic acid levels were 3- to 4-fold higher in subjects of the high-risk area. After intake of proline, the NPRO level increased (p less than 0.02) only in subjects in the high-risk area; intake of vitamin C tended to inhibit this increase in NPRO and lowered the levels of other nitrosamino acids. The urinary level of nitrates was 1.4-fold, but significantly higher among subjects in the high-risk area than among those in the low-risk area; nitrate levels were not correlated with the amounts of cured meat or types of vegetables consumed. Urinary nitrate levels and excretion of NPRO, NTCA and the sum of all nitrosamino acids analyzed showed positive, though modest, correlations. These results indicate a higher potential for endogenous nitrosamine formation, possibly by intragastric nitrosation among subjects in the high-risk rural area.

Formation of N-nitroso compounds under simulated gastric conditions from Kashmir foodstuffs

Several foodstuffs and teas from an area of high esophageal cancer risk in Kashmir (India) were studied under simulated gastric conditions with a realistic nitrite concentration for the formation of N-nitroso compounds. N-Nitrosodimethylamine (NDMA), N-nitrosoproline (NPRO), N-nitrosothiazolidine-4-carboxylic acid (NTCA) and N-nitrosopipecolic acid (NPIC) were the main products in different foods. Significant amounts of NDMA were formed from dried fish (20 μg/kg), dried and pickled vegetables (35.6 μg/kg and 7.3 μg/kg), locally grown Brassica oleracea (‘Hak’) leaves (69.9 μg/kg), and the traditional tea ‘Kehwa’ (9.2 μg/kg). The highest level of NTCA was formed in smoked fish (3294 μg/kg). ‘Salted tea’ prepared acccording to local method formed considerable amounts of NPRO (360 μg/kg) and NPIC (5870 μg/kg) along with 3 yet unidentified non-volatile N-nitroso compounds. High values of 4315 μg/kg NPIC were also obtained following nitrosation of red chillies and mixed spice cake (‘Wur’) under simulated gastric conditions. These results suggest the possibility of an appreciable endogenous formation of N-nitroso compounds from local foods in Kashmir.

Contribution of wood smoke to in vivo formation of N-nitrosothiazolidine-4-carboxylic acid: Initial studies

The effect of administering liquid smoke or smoked food products to rats on in vivo formation of N-nitrosamino acids was investigated. Rats treated by gavage with either cysteine, formaldehyde or nitrite excreted urine containing no detectable levels of N-nitrosothiazolidine-4-carboxylic acid (NTCA). All three precursor compounds were required for NTCA formation. Two liquid smokes, when administered to rats in combination with cysteine and nitrite also produced measurable quantities of NTCA. Ascorbate inhibited in vivo formation of NTCA by approximately 90% when given to rats simultaneously with cysteine, formaldehyde, and nitrite. α-Tocopherol was much less effective than ascorbate in blocking NTCA formation. When smoked bacon, smoked Swiss cheese, and chicken barbecued with a sauce containing smoke flavouring were fed to rats along with nitrate, NTCA was again detected in the urine.

Determination By Liquid Chromatography With Electrochemical Detection Of Cysteamine And Cysteine, Possible Precursors Of /V-Nitrosothiazolidine

A method is described that is selective, sensitive, rapid, and accurate for the quantitative measurement in meat products of both cysteamine and cysteine, potential precursors for N-nitrosothiazolidine (NTHZ) and N-nitrosothiazolidine-4-carboxylic acid (NTHZC), respectively. In general, a ground meat sample is homogenized with acetonitrile-formate buffer in the presence of dithiothreitol, and then is centrifuged, filtered, and recentrifuged in a disposable microfilter. The thiols are quantitated by liquid chromatography using an amperometric detector equipped with a gold/mercury electrode, operated in the oxidative mode. Cysteamine was found in 6 of 20 samples of raw pork belly in concentrations ranging from 150 to 450 ppb, and cysteine was found in all samples in concentrations ranging from 2.4 to 36.5 ppm. Analysis for the thiols and their corresponding nitrosamines--NTHZ and NTHZC--of bacon before and after processing showed no correlation between cysteamine and cysteine levels before processing nor with nitrosamine levels after processing. Liquid chromatography with electrochemical detection was found to be an extremely selective technique to measure the 2 free sulfhydryl compounds in a complex food substrate.

Computer automated structure evaluation of the carcinogenicity of N-nitrosothiazolidine and N-nitrosothiazolidine 4-carboxylic acid

N-Nitrosothiazolidine-4-carboxylic acid (NTCA), a sulphur-containing nitrosamine present in human urine, was predicted to be non-carcinogenic by CASE, the newly developed Computer Automated Structure Evaluating system. On the other hand, N-nitrosothiazolidine (NTHZ), a nitrosamine present in food products, was predicted to be carcinogenic. The putative non-carcinogenic NTCA may be metabolized to NTHZ, a predicted carcinogen.

Influence of cysteine and nitrate on the endogenous formation of N-nitrosamino acids

The excretion of N-nitrosamino acids and nitrate in 24-h urine was studied over a continuous 45-day period for a single volunteer on supplemented diet regime. Days 1–10 (normal diet), 11–20 (normal diet + 600 mg nitrate/day), 21–25 (normal diet), 26–30 (normal diet + 200 mg L-cysteine/day), 31–35 (normal diet), 36–40 (normal diet + 600 mg nitrate + 200 mg l-cysteine/day) and days 41–45 (normal diet). The presence of N-nitrosohydroxyproline (NHPRO) in human urine is reported for the first time as well as the influence of l-cysteine on the formation of N-nitrosothiazolidine-4-carboxylic acid (NTCA) and N-nitroso-2-methylthiazolidine-4-carboxylic acid (NMTCA) under a normal nitrate burden (75 mg/day) and a high nitrate burden (675 mg/day). After estimation of the amount of dietary nitrite consumed and the extent of nitrite formation by bacterial reduction of nitrate in the oral cavity, the total daily exposure to nitrite was calculated. From a total daily exposure of 7.2 mg nitrite/day from a typical European diet, 0.08% is required for the endogenous formation of N-nitrosamino acids found in urine. Under an increased nitrate burden (675 mg/day), the total exposure to nitrite was increased to 38 mg/day of which 0.14% was required for the endogenous formation on N-nitrosamino acids.

Relevance of N-nitrosamines to esophageal cancer in China.

Studies on the relevance of the N-nitrosamines to esophageal cancer in China are reviewed. Esophageal cancer is a complex and multifactorial problem. Although a causal association between nitrosamines exposure and esophageal cancer in China has not yet been rigorously established, exposure of Lin-Xian subjects to nitrosamines either directly or as a result of their in vivo formation has been detected in our study. Several N-nitrosamines (NDMA, NDEA, NMBzA, NPyr, NPip, and NSAR) in gastric juice collected from Lin-Xian inhabitants have been detected. A correlation was found between the lesions of esophageal epithelium and the amount of nitrosamines present. In addition, the amounts of N-nitrosamino acids (N-nitrosoproline, N-nitrosothiazolidine 4-carboxylic acid, NSAR, and nitrates) excreted in 24-hr urine of subjects in Lin-Xian were significantly higher than those in Fan-Xian, indicating a higher exposure to N-nitroso compound and their precursors of the inhabitants in the high-risk area. The effect of nitrosamines on human esophagus has been investigated at the cellular levels. The amounts of O6-MedG in DNA of esophageal or stomach mucosa of patients from Lin-Xian were higher than that from Europe (Lyon and Essen). The presence of O6-MedG in the human fetal esophagus cultured with NMBzA was also detected. These findings indicate that the elevated levels of O6-MedG in esophageal DNA could be the result of a recent exposure to N-nitroso compounds or a genetically determined reduced cellular capacity for repair of O6-MedG from DNA. The hyperplasia was induced in the esophagus of human fetus that cultured with NMBzA for 2 weeks to 2 months. The intervention studies of esophageal cancer in Lin-Xian have been pursued. Intake of moderate doses of ascorbic acids by Lin-Xian subjects effectively reduced the urinary levels of N-nitrosamino acids to those found in un-dosed subjects in the low-risk area. If N-nitroso compounds are formed in vivo and are among the causative factors of esophageal cancer in Lin-Xian, ascorbic acid appears to be effective in lowering the body burden of these carcinogenic compounds. Thus, the plan of chemoprevention is carried out in Lin-Xian.

Effect of iV-Nitrosothiazolidine-4-Carboxylic Acid on Formation of N-Nitrosothiazolidine in Uncooked Bacon

N-Nitrosothiazolidine-4-carboxylic acid (NTHZC) was recently identified in a variety of smoked fish and cured meat products. While the toxicological properties of NTHZC are currently unknown, it has been speculated that N-nitrosothiazolidine (NTHZ) in fried bacon may be caused in part by decarboxylation of NTHZC. A limited survey of uncooked cured meat products failed to demonstrate any correlation between levels of NTHZC and NTHZ. However, NTHZC levels were significantly higher, ranging from 8 to 1400 ppb, than the corresponding NTHZ levels, which ranged from less than 2 to 18 ppb. Decarboxylation of NTHZC to NTHZ in a model system occurs at 110 degrees C, which is significantly higher than the average bacon processing temperature of 54 degrees C, but lower than the normal frying temperature of 177 degrees C recommended for bacon. Results from both model system and frying experiments with NTHZC and its precursors suggest that NTHZC decarboxylation to NTHZ is not the principal pathway to NTHZ formation in uncooked bacon.