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OBJECTIVE To establish a method for simultaneous determination of the contents of 6 kinds of N-nitrosamines genotoxic impurities in losartan potassium raw material and its formulations. METHODS GC-MS/MS was adopted to determine 6 kinds of N-nitrosamines genotoxic impurities in losartan potassium raw material， Losartan potassium tablet， Losartan potassium capsule and Losartan potassium hydrochlorothiazide tablets， such as N-nitrosodimethylamine （NDMA）， N-nitrosodiethylamine （NDEA）， N-ethyl-N-nitroso-2-propanamine （NEiPA）， N-nitrosodiisopropylamine （NDiPA）， N-nitrosodipropylamine （NDPA） and N-nitrosodibutylamine （NDBA）. The separation was performed on SHIMADZU SH-L-17Sil MS capillary column by temperature- programmed GC， with injector temperature of 250 ℃ ， sample size of 1 μL， carrier gas of helium， and carrier flow rate of 1 mL/min. Electron ionization and multiple reaction monitoring （MRM） data acquisition mode were used， with an ion source temperature of 250 ℃ and solvent delay time of 3.1 min. RESULTS The separation among NDMA， NDEA， NEiPA， NDiPA， NDPA， NDBA and adjacent chromatographic peaks was good， and the separation rate was higher than 3.8； the linear ranges of them were 4.9-486.0， 4.9-488.5， 4.5-451.5， 6.8-683.5， 5.2-525.0 and 5.2-520.0 ng/mL（all r≥0.999 8）. The limits of quantitation were 4.86， 4.88， 4.52， 6.84， 5.25 and 5.20 ng/mL； the limits of detection were 0.97， 0.98， 0.90， 1.37， 1.05 and 1.04 ng/mL. RSDs of repeatability tests were 2.2%-5.6%（n＝6）， those of precision tests were 0.5%-1.4%（n＝6）， and those of stability tests were 1.5%-3.4%（n＝5）， respectively. Average recoveries of low-， medium- and high-concentration solution were 83.4%-103.0% （RSDs were 1.2%-6.3%， n＝3）， respectively. No one among the 6 kinds of N-nitrosamines genotoxic impurities was detected in both losartan potassium raw material and formulations. CONCLUSIONS The method is good in separation effect， highly accurate， sensitive and simple. It can be used in the determination of the 6 kinds of N-nitrosamines genotoxic impurities.
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Background N-nitrosamines, a group of by-products of drinking water disinfection, have strong cytotoxicity to mammals. N-nitrosamines in drinking water are at the ng·L−1 level, and its accurate qualitative and quantitative analysis is difficult, so it is necessary to develop a sensitive and accurate method to determine N-nitrosamines in drinking water. Objective To establish a solid phase extraction-gas chromatography tandem mass spectrometry (GC-MS/MS) method for simultaneous determination of 10 kinds of N-nitrosamines in drinking water. To apply the established method to determine the levels of 10 kinds of N-nitrosamines in drinking water in Nanjing, and to understand the pollution status. Methods Coconut charcoal solid phase extraction (SPE) cartridge and HLB Pro SPE cartridge were compared for the extraction efficiency of 10 N-nitrosamines in drinking water. A coconut charcoal SPE cartridge and a HLB Pro SPE cartridge were concatenated using a SPE connector, and then formed two combinations: coconut charcoal (top)-HLB Pro (bottom) and HLB Pro (top)-coconut charcoal (bottom), to extract the spiked samples, and combined with direct and independent elution ways to obtain the best extraction efficiency. From November to December 2021, 9 raw water, 10 finished water, and 7 tap water samples were collected from 9 municipal water supply units in Nanjing with 1 L brown glass sampling bottles. An 1.0 L drinking water sample was added with the isotope internal standard to prepare a test sample containing an isotope internal standard concentration of 25 ng·L−1. The automatic SPE instrument loaded all the 1.0 L drinking water samples to the tandem SPE cartridge of the HLB Pro (top)-coconut charcoal (bottom) at the rate of 15 mL·min−1. After extraction, the HLB Pro SPE cartridge and coconut charcoal SPE cartridge were transferred to the solid phase extraction vacuum device and eluted with 10 mL of dichloromethane respectively, then the dichloromethane eluents were combined, and concentrated to about 1.0 mL by nitrogen blowing after a small amount of the upper aqueous phase was removed. The concentrated solution was detected by GC-MS/MS and quantified by isotope internal standard method. Results The comparison of sample spike recovery experiments showed that coconut charcoal solid phase extraction (SPE) cartridge and HLB Pro SPE cartridge presented highcomplementarity for the extraction efficiency of 10 N-nitrosamines in drinking water. Using HLB Pro (top)-coconut charcoal (bottom), independent elution, and combined with eluents, the optimal extraction efficiency was obtained. Under these conditions, by GC MS/MS, the 10 N-nitrosamines showed a good linear relationship within the range of 2–50 ng·L−1, the correlation coefficients were all greater than 0.9996, the method detection limit was 0.149–0.211 ng·L−1, and the limit of quantification was 0.596–0.844 ng·L−1. At the spiked concentrations of 5.0, 15, and 30 ng·L−1, the average recoveries of the 10 kinds of N-nitrosamines were 88.0%–104.8%, and the relative standard deviations were 1.22%–4.87%. When applying the method to determine the concentrations of the 10 N-nitrosamines in Nanjing drinking water, the results showed that the 10 N-nitrosamines were positive in different degrees in raw water, finish water, and terminal water, the detection rates were 0%–100%, and the concentrations were ND–27.6 ng·L−1. Conclusion This tandem solid phase extraction-gas chromatography tandem mass spectrometry method can achieve simultaneous determination of a variety of N-nitrosamines in drinking water with high sensitivity and high throughput.
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Background Nitrosamines (NAms) are highly carcinogenic and frequently detected in drinking water systems in China, indicating potential human health risk through drinking water. Objective To analyze the distribution of NAms in drinking water in Shanghai and to evaluate relevant human health risk. Methods A total of 94 samples of source water and 120 samples of finished water were collected in February (dry period) and August (wet period) of 2021 from 30 drinking water plants in Shanghai, and eight NAms were quantitatively analyzed by gas chromatography tandem mass spectrometry after solid phase extraction. Cancer risks for different age groups caused by NAms exposure through water were evaluated using Monte Carlo probabilistic method and carcinogens risk assessment model recommended by the United States Environmental Protection Agency. Results The concentrations of total NAms in source and finished water were 12.56-65.86 ng·L−1 and 8.52-57.38 ng·L−1, respectively. The average concentration of total NAms was higher in source water (33.50 ng·L−1) than in finished water (22.07 ng·L−1, P<0.05) during dry season, and lower in source water (16.90 ng·L−1) than in finished water (21.02 ng·L−1, P<0.05) during wet season. The average concentration of total NAms in source water during dry season was twice of that during wet season. The positive rate of N-nitrosodimethylamine (NDMA) was the highest (100%) among the eight NAms. The cancer risk of exposure to NAms in finished water in Shanghai was mainly from the ingestion route, which was mostly caused by NDMA. The cancer risk from exposure to NAms in water for children (median=4.32×10−5) was slightly higher than that for adults (median=3.34×10−5) and adolescents (median=2.27×10−5). The cancer risks of exposure to NAms in water for people of different ages were mainly (80% - 95%) at an acceptable level (1×10−6 - 1×10−4). Conclusion NAms contamination is positive in Shanghai’s drinking water and NDMA is the main contaminant. The removal of NAms in water by current water treatment process is season-dependent. The cancer risk of children exposed to NAms in water was slightly higher than that of adults and adolescents, but all at acceptable levels.
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El objetivo de esta revisión es presentar el estado del conocimiento respecto a la capacidad que tiene Candida albicans de producir nitrosaminas y de cómo estas se relacionan con la posible malignización de lesiones de la cavidad bucal. La candidiasis oral (CO) es una infección frecuente de la mucosa bucal provocada por hongos de la familia Candida spp. Estos hongos son integrantes de la flora bucal habitual, pero, por diferentes factores locales y sistémicos, pueden producir micosis superficiales. Entre las distintas especies, albicans, es la más frecuente en la cavidad bucal.Posee gran variedad de factores de virulencia, uno de ellos la capacidad de nitrosación de nitratos y nitritos presentes en saliva que últimamente se ha considerado relacionada a la malignización de lesiones mucosas de la cavidad bucal y otras como el estómago.
This literature review was carried out to approach the state of knowledge regarding the capacity of Candida Albicans to produce nitrosamines and how these are related to the possible malignancy of lesions in the oral cavity. Oral candidiasis (CO) is a frequent infection of the oral mucosa caused by fungi of the family Candida spp. These fungi are part of the usual oral flora but, due to different local and systemic factors, can produce superficial mycosis. Among the different species, Albicans is the most frequent in the oral cavity. It has a great variety of virulence factors, one of them the nitrosation capacity of nitrates and nitrites present in saliva that lately has been considered related to the malignization of mucosal lesions of the oral cavity and others such as the stomach.
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@#Oral cancer is one of the most common cancers that occur in the head and neck and can seriously affect the life span and living standard of oral cancer patients. Candida albicans （C. albicans） is the most common opportunistic pathogenic fungus in the oral cavity, shows pathogenicity and easily causes Candida infection when the host′s immune function is low. Recent studies have shown that C. albicans infection is closely related to oral cancer. This paper reviews the epidemiology of C. albicans infection in oral cancer patients, the influence of C. albicans infection on the occurrence and development of oral cancer and research on its mechanism. Existing studies have shown an increased risk of C. albicans infection in oral cancer patients, while C. albicans infection may promote the occurrence and development of oral cancer through mechanisms such as damaging the oral epithelium; producing carcinogens, including nitrosamine and acetaldehyde; and inducing a chronic inflammatory response and T helper cell 17 immune response. However, these mechanisms are still relatively superficial and lack sufficient direct evidence. In the future, additional in-depth studies are still needed to further clarify the cancer-promoting mechanisms of C. albicans and provide new ideas for the prevention and treatment of oral cancer.
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Oral cancer is the most common malignant tumor in the head and neck, and is one of the world's top ten malignancies. Microbial infection is an important risk factor of oral cancer. Candida albicans is the most popular opportunistic fungal pathogen. Epidemiological studies have shown that Candida albicans is closely tied to oral malignancy. Animal experimentation have also proven that infection of Candida albicans can promote the development of oral epithelial carcinogenesis. The current studies have revealed several mechanisms involved in this process, including destroying the epithelial barrier, producing carcinogenic substances (nitrosamines, acetaldehyde), inducing chronic inflammation, activating immune response, etc. However, current researches on mechanisms are still inadequate, and some hypotheses remain controversial. Here, we review the findings related to Candida albicans' effect on the malignant transformation of oral mucosa, hoping to provide reference for deep research and controlling oral cancer clinically.
Subject(s)
Animals , Candida albicans , Carcinogenesis , Mouth Diseases , Mouth Mucosa , Mouth NeoplasmsABSTRACT
@#Recently, one of the head and neck tumours located at the nasopharynx epithelium known as nasopharyngeal carcinoma (NPC) have been associated with few cancer-promoting compounds that derived from alcohol, salt preserved foods consumptions and tobacco smoking such as acetaldehyde, nitrosamine, nicotine. These cancer-promoting compounds present the ability to damage the genome and disrupt cellular metabolic processes. This review will discuss further on the molecular mechanism of acetaldehyde, nitrosamine, nicotine and NPC risk. Acetaldehyde can exert influence as carcinogen macromolecular adducts to cellular proteins and DNAs whilst nitrosamines that commonly found in preserved salted foods/diets can contribute as a powerful carcinogen via endogenous nitrosation and reactives molecules by CYP2E1. Nicotine present in tobacco could reacts with nitrosamine to form NNN and NNK known as carcinogenic agent. NNK mediates unstable reactive oxygen species that can induce DNA lesion (α -hydroxylation of NNN at positions 2’and 5’) and microenvironment alteration for tumorigenesis. In conclusion, this study suggests acetaldehydes, nitrosamine and nicotine may contribute to NPC tumourigenesis.
Subject(s)
Nasopharyngeal CarcinomaABSTRACT
OBJECTIVES: N-Nitrosodimethylamine (NDMA) is classified as a probable human carcinogen by the United States Environmental Protection Agency (US EPA) and is formed during the chlorination of municipal drinking water. In this study, selected nitrosamines were measured in chlorinated drinking water collected from Chuncheon, Kangwon-do, Republic of Korea, and a risk assessment for NDMA was conducted. METHODS: Twelve water samples were collected from 2 treatment plants and 10 household taps. Samples were analyzed for 6 nitrosamines via solid-phase extraction cleanup followed by conversion to dansyl derivatives and high-performance liquid chromatography-fluorescence detection (HPLC-FLD). Considering the dietary patterns of Korean people and the concentration change of NDMA by boiling, a carcinogenic risk assessment from ingestion exposure was conducted following the US EPA guidelines. RESULTS: NDMA concentrations ranged between 26.1 and 112.0 ng/L. NDMA in water was found to be thermally stable, and thus its concentration at the end of boiling was greater than before thermal treatment owing to the decrease in water volume. The estimated excess lifetime carcinogenic risk exceeded the regulatory baseline risk of 10(-5). CONCLUSIONS: This result suggests that more extensive studies need to be conducted on nitrosamine concentration distributions over the country and the source of relatively high nitrosamine concentrations.
Subject(s)
Humans , Dimethylnitrosamine , Drinking , Drinking Water , Eating , Family Characteristics , Halogenation , Nitrosamines , Oligopeptides , Phosphatidylcholines , Republic of Korea , Risk Assessment , United States Environmental Protection Agency , WaterABSTRACT
Objective To investigate the widespread of the liver cancer risk factors in Wuwei city,where low-incidence for liver cancer and offer the cause clue to first-level prevention. Methods Investigate the risk factor and family history of the Wuwei city resident who wlth liver cancer by using case-control study.Estimate the liver cancer heredity mode with the method of Penrose and simple segregation analysis,calculate the degree of heritability with the metllod of Falconer,s regression.Detect the content of the resulting and promoting cancer fungi,volatility N-second nitroso compound in the meal,nitrate and nitrite in the drinking water and the vitamin C in the health adults'serum by means of culturing appraisement,experiment examination etc.Results The risk factom of liver cancer in the Wuwei city were history of viral 'hepatitis type B,kinsfolk tumor,the eating salting or mildewed foods,cirrhosis,drinking surface water,well water,or wine.By using segregation analysis and estimation of heredity mode show that the morbidity of liver cancer discrepancy to the monogenic inheritance mode,maybe the polygenic inheritance mode in Wuwei city.The h~2 of index case first degree relative was 58.74%.Picking out 8 kinds of nitrosamine,14 kinds of resulting and promoting cancer fungi from resident meal.The content of nitrate and nitrite was (38.97±3.14) mg/L,(0.086±0.043) mg/L respectively in shallow well water,the vitamin C in the health adults'serum in summer was(5.74±2.79)mg/L.Conclusion It can be seen that the history of viral hepatitis type B,kinsfolk tumor,eating salting or mildewed foods,cirrhosis,addicted to drink;higher content of nitrate and nitrite in the drinking water and strong carcinogens such as volatility N-nitroso compound in the meal,and also lackingprotection factors such as vitamin C are the risk factors of the Wuwei city resident who with liver cancer,Theinherit susceptivity is the internal environment of resulting cancer change.
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The inhibitory effect of Actinidia chinensis Planch(ACP) juice on the endogenous formation of N-nitroso compounds (NOC) in the subjects from a high-risk area for gastric cancer were observed. Total concentration of volatile N-nitrosamines(VNA)in fasting gastric juice and 24-h urinary excretion of N-nitrosoproline (NPRO) were used as indices of endogenous exposure. After iagestion of 30 ml ACP juice the average total VNA concentration was significantly decreased from 2.08?1.06?g/L to 0.42?0.43?g/L (p