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Biomedical and Environmental Sciences 1999年第1期12卷 110-115页

作者： YOGESHWER SHUKLA ALKA SINGH AND BHAWNA SRIVASTAVA(Environmental carcinogenesis Division, Industrial Toxicology Research Centre,P. O. Box 80, M. C. Marg, Lucknow-226 001, India) Industrial Toxicology Research Centre 印度

Cancer chemoprevention, a desirable and important facet of biomedical research, provides a practical approach to identify potentially useful inhibitors of cancer development, and offers an opportunity to study the mechanism of carcinogenesis. During the recent past a number of compounds have been tested for their anticarcinogenic potential specially constituents of human diet. The enzyme gamma-glutamyl transpeptidase (GGT), which catalyses the transfer of glutamyl groups of peptides to other peptides and amino acids, has been proposed as a marker of cell proliferation and neoplasia. It also serves as a tool to evaluate the carcinogenic and cocarcinogenic potential of environmental toxicants. In the present investigations, GGT activity induced by carcinogenic polycyclic aromatic hydrocarbons, viz. 7,12-dimethyl-benz(a)anthracene (DMBA) and benzo(a)pyrene (BaP) was significantly inhibited by diallylsulfide (DAS) and indole-3-carbinol (I3C) in mouse skin. DAS and I3C are constituents of garlic. A significant inhibition in GGT levels was also observed in a strong mitogen (12-o-tetradecanoyl phorbol-13-acetate) induced activity by pretreatment of DAS/I3C in mouse skin. Therefore these dietary constituents seem to be strong modifiers of chemically induced carcinogenesis.

关键词： inhibition carcinogen γ-glutamyl mouse skin

Impact of mycotoxins and their metabolites associated with food grains

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Grain & Oil Science and Technology 2023年第1期6卷 1-9页

作者： Chennappa Gurikar D.P.Shivaprasad Luis Sabillón N.A.Nanje Gowda Kaliramesh Siliveru Ramaiah University of Applied Sciences BangaloreIndia Department of Grain Science and Industry Kansas State UniversityManhattanKSUSA Department of Family and Consumer Sciences New Mexico State UniversityLas CrusesNMUSA

Mycotoxins are secondary toxic metabolites synthesized by numerous filamentous fungi including members of the genus Fusarium,Penicillium,Drechslera,Aspergillus,Claviceps,Monascum,Alternaria,Cephalosporium,Nigrospora,and Trichoderma.Among them,Aspergillus and Fusarium species are major plant pathogens recognized to induce infection and produce mycotoxins in food crops.More than 400 mycotoxins have been documented and among them,aflatoxin,fumonisins,trichothecenes,zearalenone,ochratoxin A,citrinin,ergot alkaloids,and patulin are the most prominent compounds linked to a variety of human and animal health disorders.Genus Fusarium and Aspergillus belong to a saprophytic group,which can infect and contaminate many crops at pre and post-harvest stages.Mycotoxins can have a variety of negative effects on health in both humans and animals.Mycotoxins and their metabolites can cause severe acute poisoning,which can result in death,as well as long-term negative health effects,such as cancer and immune-suppressive disorders in living beings(animals and humans).Mycotoxin contamination of agricultural goods has gained global significance,due to its toxic effects on living beings,as well as its importance to international trade.Our objective is to provide a consolidated information on the potential mycotixs in food grains and their significant impact on the health of the human beings.

关键词： Mycotoxins Aspergillus Fusarium Penicillium carcinogen Contamination Aflatoxins Fumonisins

Tobacco-specific carcinogen 4-(Methylnitrosoamino)-1-(3-pyridyl)-1-butanone(NNK) Activating ERK1/2 MAP Kinases and Stimulating Proliferation of Human Mammary Epithelial Cells

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Chemical Research in Chinese Universities 2007年第1期23卷 76-80页

作者： CHEN Zhi-bo AN Yang WANG Zhe ZHANG Bo-xun LIU Lan-ying College of Life Science Jilin University Changchun 130021 P. R. China College of Life Science and Engineering Qiqihar University Qiqihar 161000 P. R. China Department of Internal Medicine of Digestion China-Japan Union Hospital Jilin University Changchun 130033 P. R. China

Cigarette smoking is correlated with the development of various cancers. 4- （Methylnitresoamino） -1- （3-pyridyl） - 1-butanone（NNK） is one of the major tobacco-specific carcinogens in the cigarette smoke, which increases the risk of breast cancer. In the present study, it was demonstrated that NNK rapidly activated ERK1 and ERK2 MAP kinases in human normal mammary epithelial cells. It was found that there are two different routes for the activation of ERK1/2 with NNK. One is from nicotinic receptor nAchR to MEK1/2, and the other is from tyrosine kinase containing receptor to MEK1/2. The tobacco-specific carcinogen NNK shows a strong proliferative effect on normal human mammary epithelial cells and cancer mammary epithelial cells.

关键词： Mammary epithelial cells NNK ERK MAPK Nicotinic receptor nAehR Tyrosine kinase Signaling pathway carcinogen Cell proliferation

carcinogens that induce the A：T 〉 T：A nucleotide substitutions in the genome

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Frontiers of Medicine 2018年第2期12卷 236-238页

作者： Guangbiao Zhou Xinchun Zhao State Key Laboratory of Membrane Biology Institute of Zoology Chinese Academy of Sciences Bering 100101 China

Recently, Ng et al. reported that the A：T 〉 T：A substitutions, proposed to be a signature of aristolochic acid （AA） exposure, were detected in 76/98 （78%） of patients with hepatocellular carcinoma （HCC） from the Taiwan Province of China, and 47% to 1.7% of HCCs from the Chinese mainland and other countries harbored the nucleotide changes. However, other carcinogens, e.g., tobacco carcinogens 4-aminobiphenyl and 1,3-butadiene, air toxic vinyl chloride and its reactive metabolites chloroethylene oxide, melphalan and chlorambucil, also cause this signature in the genome. Since tobacco smoke is a worldwide public health threat and vinyl chloride distributes globally and is an air pollutant in Taiwan Province, the estimation of the patients＇ exposure history is the key to determine the ＂culprit＂ of the A：T 〉 T：A mutations. Apparently, without estimation of the patients＇ exposure history, the conclusion of Ng et al, is unpersuasive and misleading.

关键词： genomic signature carcinogen aristolochic acid tobacco smoke vinyl chloride hepatocellular carcinoma

Role of bacteria in carcinogenesis, with special reference to carcinoma of the gallbladder

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World Journal of Gastroenterology 2010年第43期16卷 5395-5404页

作者： Gopal Nath Anil K Gulati Vijay K Shukla Department of Microbiology Institute of Medical Sciences Banaras Hindu University Department of General Surgery Institute of Medical Sciences Banaras Hindu University

Carcinoma of the gallbladder (CaGB) is the fifth commonest gastrointestinal tract cancer and is endemic in several countries. The interplay of genetic susceptibility, infections, and life style factors has been proposed to be responsible for carcinogenesis of gallbladder. Persistence of infection leading to chronic inflammation, and production of certain toxins and metabolites with carcinogenic potentials, by certain bacteria has been speculated to be involved in the transformation of the gallbladder epithelium. Therefore, any bacteria that have evolved to acquire both of the above carcinogenic mechanisms can cause cancer. Salmonella typhi has been found to be prominently associated with CaGB. Chronic typhoid carriage (persistence) and production of mediators of chronic infl ammation and a genotoxic toxin (cytotoxic distending toxin, CdtB) are also known for this bacterium. Furthermore, the natural concentrating function of the gallbladder might amplify the carcinogenic effect of the mediators of carcinogenesis. In addition to S. typhi, certain species of Helicobacter (H. bilis and H. hepaticus) and Escherichia coli have also been implicated in carcinogenesis. As the isolation rate is verypoor with the presently available culture techniques, the existence of bacteria in a viable but non-cultivable state is quite likely; therefore, sensitive and specif ic molecular techniques might reveal the etiological role of bacterial infection in gallbladder carcinogenesis. If bacteria are found to be causing cancers, then eradication of such infections might help in reducing the incidence of some cancers.

关键词： Bacteria Chronic infl ammation carcinogen Bacterial toxins Carcinoma gallbladder DNA damage

Helicobacter species and pathogenesis of gallbladder cancer

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Hepatobiliary & Pancreatic Diseases International 2010年第2期9卷 129-134页

作者： Raghvendra Raman Mishra Mallika Tewari Hari S.Shukla Department of Surgical Oncology Institute of Medical SciencesBanaras Hindu University

BACKGROUND:Gallbladder cancer(GBC)is a rare disease but a leading cause of cancer-related death worldwide.A number of etiological factors have been implicated in the causation of GBC and pathogenic infection by bacteria is one of these. DATA SOURCES:A PubMed search on'helicobacter','gall- bladder cancer',and'biliary tract malignancies'was done on the topic,and the relevant data were collected,reviewed,and analyzed. RESULTS:Helicobacter is an epsilon proteobacterium that infects the mucosal lining of the human gastrobiliary system. Infection with helicobacter is an important risk factor for the development of cancer and the bacterium has been categorized as a group-Ⅰcarcinogen by the International Agency for Research on Cancer(IARC).These microbes enter the human body by means of contaminated food and water.Thereby they invade the tissues and produce chemical carcinogens that lead to DNA damage and subsequently a series of gene mutations transform normal cells into cancer cells.In this review,we focus our attention on the role of helicobacter in the causation of biliary tract malignancies. CONCLUSIONS:The review attempts to summarize the current available data on the role of helicobacter in the causation of GBC.There are accountable data available to suggest the role of helicobacter species in the causation of GBC although larger studies are urgently required for confirmation.

关键词： helicobacter genus gallbladder cancer DNA damage carcinogen pathogenesis

Theoretical Study on the Reaction of Thymine with Iodomehane in the Water Phase

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Chinese Journal of Structural Chemistry 2012年第2期31卷 292-298页

作者：余仕问陈广谢小光林雪飞杨思娅 School of Chemistry and Chemical Engineering Qujing Normal University Department of Chemistry Yunnan University

The reaction mechanisms of carcinogenic methylating agent iodomethane （MeI） with keto and enol tautomers of thymine （K- and E-thymine） were studied by using the B3LYP/6-311＋G （d, p） method in water phase. The solvent effects were examined using the polarizable continuum model （PCM）. Specifically, PCM single-point calculations at the same level of theory were performed in acetone and CCl4 that represent a range in nonpolarity. The calculated results show that the reaction of K-thymine with MeI is a two-step mechanism, whereas that of E-thymine is a one-step mechanism. Our calculations reveal that K-thymine is appreciably more stable than the enol form in the water phase or in the two solvents. The K- and E-form reaction barriers are 135.6 and 222.1 kJ/mol, respectively in water phase. These findings indicate that the reactions mentioned above could not occur efficiently in biological media in the absence of catalyst. Our conclusions are in agreement with the previous studies on the reactions of guanine with methyl chloride and methyl bromide.

关键词： thymine iodomethane carcinogen mechanism

Optimization of experimental conditions in studies on metabolism of 4-nitrobiphenyl

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Journal of Environmental Sciences 1998年第1期10卷 66-70页

作者： Song Ning Xu Xiao-bai Research Center for Eco Environmental Sciences Chinese Academy of SciencesBeijing 100085China

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关键词： NBP metabolism reductive carcinogen HPLC/APCI/MS.

Kinetic Studies on Hexavalent Chromium Reduction

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American Journal of Analytical Chemistry 2010年第1期1卷 25-30页

作者： Ankita Basu Bidyut Saha 不详

r(VI) is a known human carcinogen. It is a wide spread environmental contaminant as it is extensively used in different industry. The kinetic study of reduction of Cr(VI) by a known organic substance, 1-butanol in micellar media have been studied spectrophotometrically. The reduction of Cr(VI) to Cr(III) occurs in a micro- heterogeneous system in cell cytoplasm. As micelles are considered to mimic the cellular membranes, the reduction process occurring in the micellar system is considered as a model to obtain insight in to the reduction process prevailing in body systems. Micellar media is also a probe to establish the mechanistic paths of reduction of Cr(VI) to Cr(III) and the effects of some electrolytes common to a biological systems are studied to establish the proposed reaction mechanism strongly. The overall reaction follows a first order dependency on substrate and hexavalent chromium and second order dependency on hydrogen ion. Suitable surfactant &suitable concentration of electrolyte enhance the rate of the reaction.

关键词： Pollution carcinogen Cr(VI) Oxidation Kinetics Surfactant Electrolyte

Removal of hexavalent chromium by an aromatic alcohol

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Journal of Biomedical Science and Engineering 2010年第7期3卷 735-741页

作者： Ankita Basu Rumpa Saha Jayashree Mandal Sumanta Ghosh Bidyut Saha 不详

Cr(VI) is a widespread environmental contaminant and a known human carcinogen. Biosorption is a very common method to remove toxic Cr(VI) from industrial waste water. In biosorption Cr(VI) is reduced to less toxic Cr(III) and adsorbed in biosorbent as Cr(III). Effective biosorbents contain hydroxy groups;it may be aliphatic or aromatic. Kinetics of reduction of Cr(VI) by an aromatic alcohol, benzyl alcohol, (which is an important volatile component of flowers of some night blooming plants) in micellar media have been studied spectrophotometrically. Micellar media is a probe to establish the mechanistic paths of reduction of Cr(VI) to Cr(III). Effects of electrolytes are studied to support the proposed reaction mechanism. Suitable surfactant & suitable concentration of electrolyte enhance the biosorption property.

关键词： Biosorption carcinogen Kinetics Chromium (VI) Benzyl Alcohol Non Functional Surfactants Salt Effect