Smokeless tobacco (paan and gutkha) consumption, prevalence, and contribution to oral cancer / 한국역학회지

Smokeless tobacco consumption, which is widespread throughout the world, leads to oral submucous fibrosis (OSMF), which is a long-lasting and devastating condition of the oral cavity with the potential for malignancy. In this review, we mainly focus on the consumption of smokeless tobacco, such as paan and gutkha, and the role of these substances in the induction of OSMF and ultimately oral cancer. The list of articles to be examined was established using citation discovery tools provided by PubMed, Scopus, and Google Scholar. The continuous chewing of paan and swallowing of gutkha trigger progressive fibrosis in submucosal tissue. Generally, OSMF occurs due to multiple risk factors, especially smokeless tobacco and its components, such as betel quid, areca nuts, and slaked lime, which are used in paan and gutkha. The incidence of oral cancer is higher in women than in men in South Asian countries. Human oral epithelium cells experience carcinogenic and genotoxic effects from the slaked lime present in the betel quid, with or without areca nut. Products such as 3-(methylnitrosamino)-proprionitrile, nitrosamines, and nicotine initiate the production of reactive oxygen species in smokeless tobacco, eventually leading to fibroblast, DNA, and RNA damage with carcinogenic effects in the mouth of tobacco consumers. The metabolic activation of nitrosamine in tobacco by cytochrome P450 enzymes may lead to the formation of N-nitrosonornicotine, a major carcinogen, and micronuclei, which are an indicator of genotoxicity. These effects lead to further DNA damage and, eventually, oral cancer.

Smokeless tobacco (paan and gutkha) consumption, prevalence, and contribution to oral cancer / 한국역학회지

Smokeless tobacco consumption, which is widespread throughout the world, leads to oral submucous fibrosis (OSMF), which is a long-lasting and devastating condition of the oral cavity with the potential for malignancy. In this review, we mainly focus on the consumption of smokeless tobacco, such as paan and gutkha, and the role of these substances in the induction of OSMF and ultimately oral cancer. The list of articles to be examined was established using citation discovery tools provided by PubMed, Scopus, and Google Scholar. The continuous chewing of paan and swallowing of gutkha trigger progressive fibrosis in submucosal tissue. Generally, OSMF occurs due to multiple risk factors, especially smokeless tobacco and its components, such as betel quid, areca nuts, and slaked lime, which are used in paan and gutkha. The incidence of oral cancer is higher in women than in men in South Asian countries. Human oral epithelium cells experience carcinogenic and genotoxic effects from the slaked lime present in the betel quid, with or without areca nut. Products such as 3-(methylnitrosamino)-proprionitrile, nitrosamines, and nicotine initiate the production of reactive oxygen species in smokeless tobacco, eventually leading to fibroblast, DNA, and RNA damage with carcinogenic effects in the mouth of tobacco consumers. The metabolic activation of nitrosamine in tobacco by cytochrome P450 enzymes may lead to the formation of N-nitrosonornicotine, a major carcinogen, and micronuclei, which are an indicator of genotoxicity. These effects lead to further DNA damage and, eventually, oral cancer.

Characterization and Expression Analysis of Peroxiredoxin Genes in NNK-induced V79 Cells / 生物医学与环境科学（英文）

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.

Development of Urinary Bladder Pre-Neoplasia by Schistosoma haematobium Eggs and Chemical Carcinogen in Mice

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.

El consumo de nitrato y su potencial efecto benéfico sobre la salud cardiovascular / Nitrate consumption and potential beneficial effect on cardiovascular health

Vegetable consumption is associated with a lower risk of suffering cardiovascular disease and cancer, traditionally ascribed to their content in antioxidants. Recently it has been proposed that this effect may be due to the presence of nitrates in vegetables. Cardiovascular diseases are usually associated with an impaired production of nitric oxide (NO) in blood vessels. One strategy aimed to correct this defective production is to generate NO from inorganic nitrates contained in vegetables. However, it has been traditionally thought that nitrites and nitrites, as those used in curing meats and as food preservers, could generate adducts that may increase cancer risk. This paradigm is now being revisited since the evidence that vegetables rich in nitrates may have a beneficial impact on human health, particularly on cardiovascular parameters, has showed promising results, although more complete clinical evidence is needed.

El consumo de vegetales está asociado a un menor riesgo de desarrollar enfermedades cardiovasculares y cáncer, efecto que tradicionalmente se le ha atribuido a su contenido en antioxidantes. Recientemente se ha propuesto que parte de estos efectos se deberían al contenido de nitratos en los vegetales. La enfermedades cardiovasculares se asocian a una disminución en la producción del óxido nítrico (NO). Una estrategia para corregir esta producción defectuosa es generar NO a partir de nitratos inorgánicos contenidos en los alimentos. Sin embargo, se ha propuesto que los nitratos, como los usados en el proceso de curación de carnes y preservación de alimentos, podrían generar aductos cancerígenos. Este paradigma está siendo revisado y la evidencia que los alimentos ricos en nitratos pudieran tener efectos benéficos sobre la salud, particularmente sobre parámetros cardiovasculares, ha generado resultados alentadores, aunque aun se necesitan estudio clínicos más completos.

4-(Methylnitrosamino)-1-(3-pyridyl) -1-butanone induces circulating microRNA deregulation in early lung carcinogenesis / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To study the alteration of circulating microRNAs in 4-(methylnitrosamino)-1-(3-pyridyl) -1-butanone (NNK)-induced early stage lung carcinogenesis.</p><p><b>METHODS</b>A lung cancer model of male F344 rats was induced with systemic NNK and levels of 8 lung cancer-associated miRNAs in whole blood and serum of rats were measured by quantitative RT-PCR of each at weeks 1, 5, 10, and 20 following NNK treatment.</p><p><b>RESULTS</b>No lung cancer was detected in control group and NNK treatment group at week 20 following NNK treatment. The levels of some circulating miRNAs were significantly higher in NNK treatment group than in control group. The miR-210 was down-regulated and the miR-206 was up-regulated in NNK treatment group. The expression level of circulating miRNAs changed from week 1 to week 20 following NNK treatment.</p><p><b>CONCLUSION</b>The expression level of circulating miRNAs is related to NNK-induced early stage lung carcinogenesis in rats and can therefore serve as its potential indicator.</p>

Changes in Wnt pathway inhibiting factors in nitrosamine-induced esophageal precancerosis lesions and effect of gexia zhuyu decoction / 中国中药杂志

<p><b>OBJECTIVE</b>To discuss the changes in Wnt pathway inhibiting factors in esophageal precancerosis lesions induced by methyl benzyl nitrosamine (MBNA) and the effect of Gexia Zhuyu decoction.</p><p><b>METHOD</b>Wistar rats were subcutaneously injected with MBNA (3.5 mg x kg(-1) for twice per week to establish the model. Since the 1st day after the model establishment, they were orally administered with Gexia Zhuyu decoction (16, 8 mg x kg(-1)). At the 10th week, esophageal tissues were collected to observe the pathological changes of esophageal mucosa, detect SFRP1, sFRP4, Axin1, Axin2 and GSK-3β mRNA levels.by fluorescent quantitation PCR analysis and β-catenin protein level by Western blotting.</p><p><b>RESULT</b>Being induced by MBNA, rats in the model group showed slight atypical hyperplasia in the histopathological examination. Compared with the normal group, Gexia Zhuyu decoction dose high and low groups showed no significant pathomorphological and histological changes. The model group showed lower gene transcription levels of esophageal tissues sFRP1, sFRP4, Axin1 and Axin2 (P < 0.05 or P < 0.01) and higher β-catenin protein expression level (P < 0.01) than the normal control group. The Gexia Zhuyu decoction low dose group showed higher gene transcription levels of esophageal tissues sFRP1, sFRP4, Axin1 and Axin2 (P < 0.05 or P < 0.01) and lower β-catenin protein expression level (P < 0.01) than the normal control group.</p><p><b>CONCLUSION</b>Up-regulated β-catenin protein level and down-regulated Wnt pathway could enhance Wnt pathway activity of MBNA-induced esophageal precancerous lesions. Gexia Zhuyu decoction could down-regulate the β-catenin protein level and up-regulate the transcription level of Wnt pathway inhibiting factors, but could not block MBNA-induced esophageal precancerosis lesions.</p>

Determination of volatile nitrosamines in urine through gas chromatography-mass spectrometry / 中华预防医学杂志

<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>Target 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.</p><p><b>RESULTS</b>A 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.</p><p><b>CONCLUSIONS</b>A gas chromatography-mass spectrometry detect method was developed for low level volatile nitrosamines in urine samples.</p>

Study on eliminating sodium nitrite and blocking nitrosamine synthesis by anthocyanin from skin of Alpinia galanga / 中国中药杂志

This study was performed to determine the ability of eliminating sodium nitrite and blocking nitrosamine synthesis by anthocyanin from the skin of Alpinia galanga. purified by macroporous resin. The test was conducted under the condition of the simulated human gastric juice (pH 3.0, 37 degrees C) with VitC as positive control. The results showed that the max capability of eliminating sodium nitrite was 87.14%, which is 1.6 times sronger than that of VitC, and the max capability of blocking nitrosamine synthesis was 97.82%, which is 8 times sronger than that of VitC.

Ocorrência de nitratos e nitritos em queijos minas frescal, mussarela, parmesão e prato / Ocurrence of nitrate and nitrite in cheeses minas frescal, mozzarella, parmesan and prato

Neste trabalho foram avaliados os teores de nitratos e nitritos em queijos expostos à venda no Estado de Minas Gerais em 2009. As análises qualitativas e quantitativas foram realizadas em 77 amostras de queijos: Minas Frescal, Mussarela, Parmesão e Prato, coletadas pela Vigilância Sanitária por meio de PROMAC –Programa de Monitoramento de Aditivos e Contaminantes. Do total de amostras de queijo Minas Frescal, 7 apresentaram não conformidade com a legislação brasileira, em função da presença de nitrato. Os teores de nitrato estavam acima do limite estabelecido pela legislação em 18 das amostras de queijo Parmesão. No queijo Prato foram encontradas 10 das amostras com teor de nitrato acima do limite máximo permitido. Todas as amostras de queijo Mussarela avaliadas estavam em conformidade com a legislação. Em todas as amostras de queijo analisadas neste estudo não houve ocorrência de nitrito.

O uso de nitrato e nitrito em produtos cárneos e a formação de N-nitrosaminas / The use of nitrate and nitrite in meat products and the formation of N-nitrosamines

A função dos sais de nitrato e nitrito em produtos cárneos está relacionada à preservação contra micro-organismos patogênicos, ao desenvolvimento e fixação da cor, flavor e inibir os processos autooxidativos. Tem sido descrito que estes sais são causadores de efeitos tóxicos agudos e crônicos se ingerido em excesso, além de ser uma das substâncias precursoras de N-nitrosaminas. Este trabalho descreve os mecanismos de ação destes sais em processos de cura, dados de residual em produtos cárneos e as reações com aminas para a formação de N-nitrosaminas. O controle da adição destes sais deveria ser na quantidade adicionada, tendo em vista ser esta a forma de inibição de C.botulinum. A avaliação do teor residual destes sais é um dos indicativos da existência de boas práticas de fabricação. As N-nitrosaminas podem ser formadas apenas a partir da reação de aminas secundárias em temperaturas elevadas e os efeitos negativos do uso destes sais são muitos superiores, quando comparados com a pequena possibilidade de formação de N-nitrosaminas. Pesquisas têm sido desenvolvidas para distribuição destes compostos. Os efeitos positivos são fatores que contribuem para uma difícil substituição em curto prazo.

Ingestion Exposure to Nitrosamines in Chlorinated Drinking Water

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.

Investigation on relationship between flavonoid content and inhibitory ability to nitrosamine synthesis for eleven Chinese herbal medicines / 中国中药杂志

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.

Fumonisin as a risk factor to esophageal cancer: a review

Among several types of cancer, esophageal is the sixth most common type found worldwide, with variable incidence rates that are more prevalent in Western countries and in South Central Asia. In Brazil, this neoplasm represents 2 percent of all malignant tumors and is the fifth leading cause of death. Brazilian estimated data demonstrated that, in 2008, the incidence of this cancer will be 7,900 cases in men and 2,650, in women, which corresponds to crude mortality rates of 8.35/100,000 and 2.72/100,000, respectively. Literature data has demonstrated several risk factors to esophageal cancer, such as: the consumption of tobacco, alcohol, hot beverages; malnutrition; obesity and gastric esophageal reflux, which causes Barrett´s esophagus. Fumonisins play significant roles in this neoplasm. Fumonisins are substances found in moldy foods, which are potential sources of nitrosamines, and are present in moldy corn. This substance was isolated in regions with high incidence of esophageal cancer in 1988, and currently is considered an important risk factor to esophageal cancer.

O papel das enzimas CYP2A na susceptibilidade ao câncer do esôfago e sua regulação / The role of CYP2A enzymes in susceptibility to esophageal cancer and its regulation

As nitrosaminas são pré-carcinógenos presentes no cigarro e em alguns alimentos e são os únicos compostos capazes de induzir tumores no esôfago de animais experimentais. Uma vez que as nitrosaminas somente se tornam cancerígenos após serem metabolizadas por enzimas CYP, a presença de um CYP capaz de ativá-las é fundamental para a susceptibilidade tecidual à indução de tumores por estes carcinógenos. A indução de tumores esofágicos pelas nitrosaminas varia entre os animais experimentais, sendo o rato a espécie mais susceptível. Em 2001, nosso grupo identificou o CYP2A3 como sendo a principal enzima responsável pela ativação da NDEA no esôfago de ratos. Por outro lado, nenhuma das nitrosaminas testadas até o momento induz tumores esofágicos no hamster, sendo o fígado o principal órgão-alvo. Com o objetivo de achar uma explicação mecanística para a resistência do esôfago do hamster às nitrosaminas, neste trabalho nós caracterizamos a expressão de enzima CYP2A no esôfago deste animal e comparamos o metabolismo da NDEA entre esôfago e fígado. Mostramos que tanto o esôfago quanto o fígado expressam os mRNAs dos CYP2A8, CYP2A9 e CYP2A16. A expressão protéica, no entanto, é diferente entre os tecidos. Os resultados de Western blotting mostram que, apesar do esôfago e fígado expressarem uma isoforma em comum, o esôfago expressa uma segunda isoforma que não é presente no fígado, enquanto o fígado expressa uma proteína que não é detectada no esôfago. Surpreendentemente, também detectamos uma alta ativação da NDEA pelos microssomos esofágicos. Porém, a eficiência catalítica desta reação foi cerca de 40 vezes menor do que a detectada nos microssomos hepáticos. Um anticorpo anti-CYP2A6 humano foi capaz de inibir o metabolismo da NDEA em microssomos esofágicos, mas não hepáticos. A diferença na eficiência catalítica da reação de NDEA entre esôfago e fígado pode explicar porque as nitrosaminas nunca induzem tumores esofágicos em hamsters. Devido ao papel dos CYP2A...

Nitrosamines are pre-carcinogens found in food and cigarette smoke and are the only compounds known to induce esophageal tumors in experimental animals. Nitrosamines become active carcinogens tumors only after being metabolized by CYP enzymes. Therefore, CYP expression is essential for tissue-specific tumor induction by nitrosamines. Esophageal tumor induction by nitrosamines varies amongst experimental animals, with the rat being the most sensitive species. We have previously shown that CYP2A3 is expressed in the rat esophagus and that CYP2A3 is responsible for NDEA activation in this tissue. On the other hand, none of the nitrosamines tested so far induces esophageal tumors in hamsters, with the liver being the main target-organ for nitrosamine induced tumors. In order to find a mechanistic explanation for its esophageal resistance to nitrosamines, we have characterized CYP2A expression in hamster esophagus and liver and compared NDEA metabolism between these tissues. Hamster esophagus and liver express CYP2A8, CYP2A9 and CYP2A16 mRNAs. However, protein expression is different between the tissues, and our Western blotting results showed that, whereas both the esophagus and liver express two CYP2A isoforms each, only one of the isoforms is similar in both tissues. Surprisingly, we have detected a high NDEA activation in the esophageal microsomes. However, the catalytic efficiency for this reaction was about 40-fold lower than the one detected for hepatic microsomes. An antibody against human CYP26 was able to inhibit NDEA in hamster esophageal, but not liver microsomes. The difference in the catalytic efficiency towards NDEA metabolism between esophagus and liver could help to explain hamster esophageal resistance to nitrosamines. CYP2A inhibition could be a promising approach in chemoprevention, leading to a reduction of the diseases associated with tobacco smoking. There are few data about CYP2A inhibition in experimental animals...

Enhancive effect of N,N'-dinitrosopiperazine on inducing precancerous lesion on nasal and/or nasopharyngeal epithelia of TgN(p53mt-LMP1)/HT mice / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

<p><b>OBJECTIVE</b>To investigate the enhancive effect of N,N'-dinitrosopiperazine (DNP) on induced carcinogenesis in nasal and/or nasopharyngeal epithelia among TgN(p53mt-LMP1)/HT transgenic mice to examine the underlying mechanism for the development of nasopharyngeal carcinoma (NPC).</p><p><b>METHODS</b>TgN(p53mt-LMP1)/HT transgenic mice and the same strain of C(57)BL/6J wild-type mice both at the age of 5 months were randomly divided into 2 groups in parallel, respectively, i.e., TgN(p53mt-LMP1)/HT cancerous lesion-inducing group (TI), TgN(p53mt-LMP1)/HT control group (TC), C57BL/6J cancerous lesion-inducing group (CI), and C57BL/6J control group (CC). TI and CI mice were treated only with DNP for 16 weeks, twice each week, while TC and CC mice were given the same volume of saline as controls. At the end of treatment, animals were sacrificed to collect epithelial tissue samples from nasal cavity and nasopharynx for pathohistological evaluation by haematoxylin and eosin (HE) staining and for determination on the expression of TRAF2, c-Jun, and p16 by immunohistochemistry.</p><p><b>RESULTS</b>Atypical hyperplasia was more significant in the samples of TI than in those of TC, CI, and CC, with the rates of lesions being 90%, 10%, 0, and 0 (P<0.01) respectively, though DNP was used alone in a much shortened inducing period at less dosage and without the use of carcinogenic promoter 12-O-tetradecanoylphorbol-13-acetate as usual. The expressions of tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) and c-Jun in these samples were significantly up-regulated in TI (P<0.01), while the expression of p16 was significantly lower in TI than in the other groups (P<0.01).</p><p><b>CONCLUSION</b>TgN(p53mt-LMP1)/HT mice hold inherited constitutional defect in immune surveillance function, which can be aggravated by environmental carcinogens, such as DNP used even though in a much less strength. The enhanced carcinogenesis-inducing effect of DNP on TgN(p53mt-LMP1)/HT mice should be closely associated with abnormal signaling of activator protein-1 (AP-1) pathway, especially up-regulated expressions of TRAF2 and c-Jun, and down-regulated expression of p16.</p>

Toxicity and carcinogenicity of ozone in combination with 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone and dibutyl phthalate in B6C3F1 mice for 16 and 32 weeks / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To evaluate the toxic and carcinogenic potential of ozone alone or in combination with 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and/or dibutyl phthalate (DBP).</p><p><b>METHODS</b>Male and female B6C3F1 mice were exposed, through inhalation, intravenous administration and diet, to 0.5 ppm of ozone, 1.0 mg/kg of NNK and 5000 ppm of DBP, individually and in combination for 16 and 32 weeks.</p><p><b>RESULTS</b>No treatment-related death was seen, but significant differences in body and organ weights between control and treated mice were observed during the study. No incidence of lung tumor incidence was recorded in mice exposed to either ozone alone or combined treatment. Oviductal carcinomas were observed in female mice exposed to ozone or DBP alone for 16 weeks and ozone in combination with NNK and DBP for 32 weeks.</p><p><b>CONCLUSION</b>Although ozone alone and in conjunction with NNK and/or DBP does not induce lung cancer under our experimental conditions, they induce oviductal carcinomas in B6C3F1 mice.</p>

Effects of Extremely Low Frequency Elecromagnetic Fields on Thyroid Carcinogenesis Induced by N-bis(2-hydroxypropyl)nitrosamine and Sulfadimethoxine

PURPOSE: Long-term exposure to extremely low-frequency (60 Hz) electromagnetic fields (ELF-EMF) raises the questions of the induction of biological effects including tumorigenesis. One mechanism through which ELF-MFS could influence neoplastic development is the imbalance of cellular proliferation and cell apoptosis. The present study investigated the effect of ELF-EMF on chemically-induced thyroid carcinogenesis in a rat. METHODS: We examined cellular proliferation index measured by anti-Ki-67 antigen, apoptosis, apoptosis related proteins such as caspase 3 and p53, and cell cycle-related proteins (cyclin D1 and p21(WAF1/Cip1)). Forty Male F344 rats received a subcutaneous N-bis(2-hydroxypropyl)nitrosamine (DHPN, 2,800 mg/kg) injection, and 1 week later were allowed free access to drinking water containing sulfadimethoxine (0.1%) for 12 weeks. Twenty rats were exposed by ELF-EMF. During the carcinogenesis, sequential histological changes from hyperplasia, adenoma, and ultimately to overt carcinomas were noted. RESULTS: The exposure group of ELF-EMF, significantly increases the number size of carcinomas. Also, the proliferative and apoptotic indices were significantly increased in the ELF-EMF exposure group than in the control group. The caspase 3 protein expression did not show any significant changes between ELF-EMF group and control group. The p53 protein was not detected in both ELF-EMF exposure and control group. Among the cell cycle related proteins, cyclin D1, not p21(WAF1/Cip1), was significantly increased in adenomas and carcinomas in ELF-EMF exposure group compared with the control group. CONCLUSION: Exposure of ELF-EMF effects on chemically-induced rat thyroid carcinogenesis as results of altered increase of cellular proliferation, apoptosis, and cyclin D1 expression.

Nitratos, nitritos, nitrosaminas e seus efeitos sobre o organismo humano / Nitrates, nitrites, nitrosamines and their effects on the human body

Os nitratos e nitritos, na forma de sal de sódio e potássio, são largamente usados no processamento de derivados cárneos, originando produtos como presuntos, bacon e salsichas. São conservantes geralmente adicionados aos sais de cura, sendo responsáveis pela formação e estabilidade da cor de produtos cárneos, possuindo também atividade antimicrobiana. O nitrito pode ser adicionado diretamente na carne ou ser obtido através da redução do nitrato na própria carne, por ação de bactérias redutoras. Os nitratos são pouco tóxicos, a não ser em níveis elevados, porém, os nitritos possuem uma toxicidade maior, pois são capazes de se combinar com compostos presentes nos alimentos formando compostos nitrosos denominados nitrosaminas. Como a maioria desses compostos têm apresentado atividade cancerígena e mutagênica, a sua formação e ocorrência estão sendo cada vez mais estudadas com o propósito de se conhecer melhor esse tipo de contaminante e os riscos potencialmente envolvidos com a sua ingestão. A utilização destes conservantes em concentrações adequadas e rigorosamente controladas, associada com a avaliação da sua ingesta pela população, possibilita minimizar a possibilidade de ocorrência de problemas de toxidade pelo seu consumo. Com isso tem-se uma maneira de diminuir os riscos sofridos pelos consumidores de produtos cárneos curados.

Qualidade físico-química de corned beef produzido por um estabelecimento situado em Barretos, SP / Phisical-chemical quality of corned beef produced in an establishment in Barretos, SP

O objetivo deste trabalho foi avaliar a qualidade do corned beef comercializado no Brasil e exportado para outros países. O teorde proteínas, a umidade e a relação entre estes parâmetros e o teor de nitrito residual foram analisados usando-se técnicasoficiais. Cinqüenta e duas amostras provenientes de um estabelecimento aprovado para comércio local e internacional,situado em Barretos, estado de São Paulo, foram estudadas. O teor de proteínas variou de 23,75 a 29,35 por cento (26,49±1,11) e aumidade de 52,31 a 59,98 por cento (56,70±1,48) atendendo às exigências tecnológicas para produtos cárneos industrializados. Oteor de nitrito residual variou de 0,88 a 8,74 ppm (5,34±1,83). Conclui-se que o produto está de acordo com os padrões físico-químicos da legislação brasileira.

The objective of this study was to evaluate the quality of corned beef that is commercialized in Brazil and exported to othercountries. The protein, humidity and the relation between these parameters and residual nitrite levels were analyzed accordingto official techniques. Fifty-two samples from an approved establishment to local and international commerce, located inBarretos, São Paulo State, were analyzed. The protein content range of 23.75 to 29.35 percent (26.49±1.11) and the humidity from52.31 to 59.98 percent (56.70±1.48). Relation between these parameters attended to the technological parameters requirements forindustrialized meat products. The residual nitrite levels varied from 0.88 to 8.74 ppm (5.34±1.83). It can be concluded that theproduct is according to the Brazilian physical-chemical standards legislation.