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.
Dimethylnitrosamine ; Drinking ; Drinking Water ; Eating ; Family Characteristics ; Halogenation ; Humans ; Nitrosamines ; Oligopeptides ; Phosphatidylcholines ; Republic of Korea ; Risk Assessment ; United States Environmental Protection Agency ; Water

The modifying potential of capsaicin (CAP) on lesion development was examined in a rat multiorgan carcinogenesis model. Groups 1 and 2 were treated sequentially with diethylnitrosamine (DEN) (100 mg/kg, ip, single dose at commencement), N-methylnitrosourea (MNU) (20 mg/kg, ip, 4 doses at days 2, 5, 8, and 11), and N,N-dibutylnitrosamine (DBN) (0.05% in drinking water during weeks 3 and 4). Group 3 received vehicles without carcinogens during the initiation period. Group 4 served as the untreated control. After this initiating procedure, Groups 2 and 3 were administered a diet containing 0.01% CAP. All surviving animals were killed 20 weeks after the beginning of the experiment and the target organs examined histopathologically. The induction of GST-P+ hepatic foci in rats treated with carcinogens was significantly inhibited by treatment with CAP. CAP treatment significantly decreased the incidence of adenoma of the lung but increased the incidence of papillary or nodular (PN) hyperplasia of the urinary bladder. The tumor incidence of other organs, such as the kidney and thyroid, was not significantly different from the corresponding controls. These results demonstrated that concurrent treatment with CAP not only can inhibit carcinogenesis but can also enhance it depending on the organ. Thus, this wide-spectrum initiation model could be used to confirm organ-specific modification potential and, in addition, demonstrate different modifying effects of CAP on liver, lung, and bladder carcinogenesis.
Animals ; Capsaicin/pharmacology/*toxicity ; Cocarcinogenesis ; Diethylnitrosamine ; Liver Neoplasms, Experimental/chemically induced/prevention & control ; Lung Neoplasms/chemically induced/prevention & control ; Male ; Methylnitrosourea ; Neoplasms, Experimental/*chemically induced/prevention & control ; Nitrosamines ; Rats ; Rats, Inbred F344 ; Urinary Bladder Neoplasms/chemically induced

Schistosoma haematobium is a biocarcinogen of human urinary bladder (UB). The present study investigated developing UB cancer mouse model by injecting S. haematobium eggs into the bladder wall and introduction of chemical carcinogens. Histopathological findings showed mild hyperplasia to epithelial vacuolar change, and high grade dysplasia. Squamous metaplasia was observed in the S. haematobium eggs+NDMA group at week 12 but not in other groups. Immunohistochemistry revealed significantly high expression of Ki-67 in urothelial epithelial cells of the S. haematobium eggs+BBN group at week 20. The qRT-PCR showed high expression of p53 gene in S. haematobium eggs group at week 4 and S. haematobium eggs+BBN group at week 20. E-cadherin and vimentin showed contrasting expression in S. haematobium eggs+BBN group. Such inverse expression of E-cadherin and vimentin may indicate epithelial mesenchymal transition in the UB tissue. In conclusion, S. haematobium eggs and nitrosamines may transform UB cells into squamous metaplasia and dysplasia in correlation with increased expression of Ki-67. Marked decrease in E-cadherin and increase in p53 and vimentin expressions may support the transformation. The present study introduces a promising modified animal model for UB cancer study using S. haematobium eggs.
Animals ; Cadherins ; Carcinogens ; Dimethylnitrosamine ; Eggs* ; Epithelial Cells ; Epithelial-Mesenchymal Transition ; Genes, p53 ; Humans ; Hyperplasia ; Immunohistochemistry ; Metaplasia ; Mice* ; Models, Animal ; Nitrosamines ; Ovum* ; Schistosoma haematobium* ; Schistosoma* ; Urinary Bladder Neoplasms ; Urinary Bladder* ; Vimentin

OBJECTIVETo establish a detection method based on gas chromatography-mass spectrometry (GC-MS) for concentrations of volatile nitrosamine compounds in urine, and apply it to the test of real samples.

METHODSTarget compounds dichloromethane in urine samples was extracted with dichloromethane through liquid-liquid extraction, then the dichloromethane extract was filtrated, evaporated with nitrogen at 40°C to dryness, and the volume was set with 0.2 ml dichloromethane. Analysis of nine volatile nitroso-compounds were performed with GC-MS under selected ion monitoring mode, external reference method was used for quantification, and the detection limit, repeatability and sensitivity were evaluated. In addition, nine volatile nitroso-compounds of 92 urine samples in a town of Anhui province were measured.

RESULTSA good linear range of 2 - 200 ng/ml (with correlation coefficient 0.9985 - 0.9999) were obtained for the above mentioned nine kinds of analyte, and the lowest examination concentration was 0.05 - 0.50 ng/ml. The addition standard recoveries were 68%-102% with the RSD of 0.4% - 5.5% (n = 3). The detection limits were 0.001 - 0.013 ng/ml urine. The detection rate of N-nitrosodimethylamine (NDMA), N-nitrosomethylethylamine (NMEA), N-nitrosodiethylamine (NDEA), N-nitrosodi-n-propylamine (NDPA), N-nitrosopyrrolidine (NPYR), N-nitrosomorpholine (NMOR), N-nitrosopiperidine (NPIP), N-nitrosodi-n-butylamine (NDBA) and N-nitrosodiphenylamine (NDPhA) were 71% (65), 74% (68), 65% (60), 80% (73), 92% (85), 78% (72), 76% (70), 87% (80), 98% (90), respectively, with the results (0.27 ± 0.12), (0.75 ± 0.29), (0.06 ± 0.02), (0.16 ± 0.07), (23.66 ± 5.18), (1.01 ± 0.35), (0.38 ± 0.11), (2.47 ± 0.52) and (15.13 ± 3.48) nmol/g creatinine.

CONCLUSIONSA gas chromatography-mass spectrometry detect method was developed for low level volatile nitrosamines in urine samples.

Gas Chromatography-Mass Spectrometry ; Humans ; Nitrosamines ; urine ; Urinalysis ; methods ; Volatile Organic Compounds ; urine

The eleven Chinese herbal medicine containing flavonoids are applied as raw materials to explore the relationship between the inhibitory ratio of nitrosamine synthesis, the scavenging ratio of nitrite and the flavonoid content in the samples. The inhibitory ratio of nitrosamine synthesis and the scavenging ratio of nitrite of the 11 herbal medicines, Vit C and rutin were determined in intro compare with Vit C and the standard ample of rutin. The results indicate that each sample exhibits certain ability to inhibitiory nitrosamine synthesis. Among these samples, Honeysuckle flower is found to be of best effects, its inhibitory ratio and scavenging ratio reaches 78.5% and 60.5%, respectively. Except kudzuvine root, the other samples with higher content of flavonoid result in a higher inhibitory or scavenging ratio, and the relative coefficient reaches a value of 0.9338 and 0.9272, respectively, displaying notable positive correlation. The concentrations of IC50 (g x L(-1)) of flavonoid extracted from honeysuckle, rutin and VC were 0.013, 0.022 and 0.187, respectively. While the inhibitory ratio of synthesis of nitrosamines reached 50%, and those were 0.042, 0.024 and 0.041, respectively. While scavenging ratio of nitrite reaches 50%. The inhibitory ratio of synthesis of nitrosamine of flavonoids extracted from honeysuckle flower is higher than that of Vit C and rutin, and the scavenging ratio of nitrite is similar to that of Vit C.
Drug Interactions ; Drugs, Chinese Herbal ; analysis ; pharmacology ; Flavonoids ; analysis ; pharmacology ; Nitrosamines ; chemical synthesis ; pharmacology ; Plants, Medicinal ; chemistry

The ultrastructural alterations in rat liver by feeding NHM(nitrosohexamethylenemine). These are described at intervals of 10 days, 5 weeks, 11 weeks, 14 weeks, 19 weeks, and 22 weeks. The group at 5 and 11 weeks showed hyperplastic lesions but, no nuclear change. There were dilated rough endoplasmic reticulum with detached ribosomes, and alteration of mitochondria. The mitochondria showed a dense matrix which often included membranous materials. In the l4, 19, and 22 week groups, it showed nodular lesion which had atypical cells, and it was observed that the nucleus were enlarged and nucleoli were segregated. The bile canaliculi were dilated and contained dense materials.
Animal ; Female ; Liver/drug effects* ; Liver/pathology ; Methenamine/pharmacology* ; Microscopy, Electron ; Mitochondria, Liver/drug effects ; Nitrosamines/pharmacology ; Nitroso Compounds/pharmacology* ; Rats

The effect of four alkylating agents (MMS, EMs, DMN, DEM), under various con centrations on mouse bone marrow erythrocytes, were studied by means of the micronucleus test. The results obtained were as follows: 1) The lethal doses on mice were MMS = 130 mg/kg/bw, EMS = 300 mg/kg/bw, DMN = 50 mg/kg/bw and DEN = 70 mg/kg/bw. 2) Micronuclei were easily seen and in different controls the micronulei were found a little over 0.1%. 3) The dose-effect relationship was obtained. In the MMS and EMS treated groups, incidences of micronulei were 0.45 to 2.56% and 0.4 to 2.1% respectively. 4) In the DMN and DEN treated groups, incidences varied between 0.15 to 0.90 % and 0.2 to 1.02% respectively. 5) Four alkylating agents were compared and discussed with respect to micro nucleus production from chromosomal aberrations.
Animal ; Bone Marrow/ultrastructure ; Carcinogens/pharmacology* ; Cell Nucleus/drug effects* ; Chromosome Aberrations* ; Erythrocytes/ultrastructure ; Female ; Mesylates/pharmacology* ; Mice ; Mutagens/pharmacology ; Nitrosamines/pharmacology*

OBJECTIVENan'ao County in Guandong Province is a high-risk area of esophageal cancer in Southern China. Of the suspected etiological factors in the environment, N-nitrosamines and their precursors have received the greatest attention.

METHODSSixty samples of the diet ingested by the inhabitants were collected and detected for volatile N-nitrosamines and their precursors. Five N-nitrosamines detected by Gas Chromatography-Thermal Energy Analyzer were N-nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosopyrrolidine, N-nitrosopiperidine and N-nitrosomethyl-benzylamine.

RESULTSThe average content of 5 volatile N-nitrosamines in the diet was 312.0 micrograms/kg (median). The daily intake of the nitrosamines was 286.5 micrograms/head/day. Only the ability to exogenously synthesize N-nitrosopiperidine was powerful among 5 volatile N-nitrosamines. By a computerized stepwise regression analysis and curve fitting, we studied the correlation among the nitrosamines, the precursors and the major food items in the samples.

CONCLUSIONIt demonstrated that a relatively high content of volatile N-nitrosamines was present in the diet collected in the area.

Adult ; China ; epidemiology ; Diet ; Esophageal Neoplasms ; epidemiology ; etiology ; Female ; Humans ; Male ; Middle Aged ; Nitrosamines ; administration & dosage ; adverse effects ; Risk Factors ; Volatilization

OBJECTIVETo establish an in vitro heterogeneous expression model of human CYP2E1 (hCYP2E1) cDNA and investigate the effect of the chemical carcinogenic N, N'-dinitrosopiperazine (DNP) on the expression of CYP2E1.

METHODSExogenous hCYP2E1 was introduced into the mouse derived NIH3T3 cells using the lipofectamine transfection technique. Integration of exogenous hCYP2E1 gene was identified by PCR and Southern blot. After treatment with various concentration of ethanol and DNP on the transfected NIH3T3 cell cultures, RT-PCR and Western blot was applied to detect the expression level of CYP2E1.

RESULTSTwo cell clones with integration and stable expression of exogenous hCYP2E1 were obtained and designated as NIH3T3-2E1-A4 and NIH3T3-2E1-A8 respectively. The expression of both hCYP2E1 mRNA and protein products was promoted after either ethanol or DNP treatment.

CONCLUSIONThe results suggested that the promoted expression of hCYP2E1 induced by DNP and /or ethanol is due to enhanced transcription. The mechanism of DNP carcinogenes is might be related to this in situ activated metabolism by CYP2E1.

3T3 Cells ; Animals ; Carcinogens ; toxicity ; Cytochrome P-450 CYP2E1 ; genetics ; Ethanol ; pharmacology ; Gene Expression Regulation, Enzymologic ; drug effects ; Humans ; Mice ; Nitrosamines ; toxicity ; Reverse Transcriptase Polymerase Chain Reaction ; Transfection

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent and prevalent nitrosamine procarcinogen found in cigarette smoke. The aim of this work is to study alterations in peroxiredoxin (Prx) expression induced by NNK during carcinogenesis. Characterization of Prx genes from hamster was performed using bioinformatics. V79 cells were induced with different concentrations of NNK (0.1-0.4 mg/mL), and the expression levels of six Prx genes (Prx1-Prx6) were measured by qRT-PCR 24 h following NNK treatment. Prx gene expression was induced by NNK stress, and the highest transcription levels were induced by over 20.42-fold relative to that of the control. NNK induced alterations in Prx expression over the course of lung cancer, which means Prxs may play important roles in ROS detoxification under NNK stress and their functions are complementary.
Animals ; Carcinogens ; administration & dosage ; toxicity ; Cell Line ; Cell Survival ; Cricetinae ; Cricetulus ; Dose-Response Relationship, Drug ; Gene Expression Regulation ; drug effects ; Nitrosamines ; administration & dosage ; toxicity ; Peroxiredoxins ; genetics ; metabolism