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The Effects of Dietary Restriction and Aging on in Vivo and in Vitro Binding of Aflatoxin B_1 to Cellular DNA

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Biomedical and Environmental Sciences 1991年第1期4卷 134-143页

作者： MING W.CHOU REX A.PEGRAM PU GAO S.R.HANSARD J.G.SHADDOCK D.A.CASCIANO national center for toxicological research JeffersonNational Center for Toxicological Research JeffersonNational Center for Toxicological Research JeffersonNational Center for Toxicological Research JeffersonNational Center for Toxicological Research JeffersonNational Arkansas AR 72079 To whom repucsts for reprints should be addressed Arkansas AR 72079 US EPA HERL MD-74 Research Triangle Park NC 27711 Arkansas AR 72079 Arkansas AR 72079Arkansas AR 72079Center for Toxicological Research Jefferson Arkansas AR 72079

Laboratory animals maintained on a reduced calorie but nutritionally adequate diet have extended life spans and lowered incidences of spontaneous and chemically induced cancers compared to ad libitum- fed counterparts. Many of the effects of dietary restriction on laboratory animals have been suggested to be related to a deceleration of the aging process. The inhibition of age-related changes in xenobiotic metabolizing enzyme activities by dietary restriction has previously been reported. Alterations of these enzyme activities may cause changes in metabolic activation of carcinogens and, therefore, carcinogen-DNA binding. DNA-repair capability has also been reported to be enhanced in diet-restricted rats. Using AFB1 as a model carcinogen, we have studied in vivo and in vitro hepatic AFB1 -DNA binding, demonstrating that dietary restriction (60% of ad libitum consumption) may decrease the metabolic activation of AFB1, and subsequently reduce AFB 1-DNA binding. Our preliminary results obtained from the AFB 1-DNA binding experiments in isolated hepatocytes suggest that the observed age-dependent reduction in AFB 1-DNA binding which may be attributed to a loss of metabolic activating capability was delayed in the diet-restricted rats.

关键词： The Effects of Dietary Restriction and Aging on in Vivo and in Vitro Binding of Aflatoxin B1 to Cellular DNA AFB

Studies on abacavir-induced hypersensitivity reaction:a successful example of translation of pharmacogenetics to personalized medicine

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Science China(Life Sciences) 2013年第2期56卷 119-124页

作者： GUO YongLi SHI LeMing HONG HuiXiao SU ZhenQiang FUSCOE James NING BaiTang Division of Systems Biology National Center for Toxicological Researchthe US Food and Drug Administration Division of Bioinformatics and Biostatistics National Center for Toxicological Researchthe US Food and Drug Administration

Abacavir is an effective nucleoside analog reverse transcriptase inhibitor used to treat human immunodeficiency virus(HIV) infected *** main side effect is hypersensitivity reaction(HSR).The incidence of the HSR is associated with ethnicity among patients exposed to abacavir,and retrospective and prospective studies show a significantly increased risk of abacavir-induced HSR in human leukocyte antigen(HLA)-B*57:01-carrying *** studies indicated that abacavir interacts specifically with HLA-B*57:01 and changed the binding specificity between the HLA molecule and the HLA-presented endogenous peptide repertoire,leading to a systemic autoimmune ***-B*57:01 screening,combined with patch testing,had clinically predictive value and cost-effective impact in reducing the incidence of abacavir-induced HSR regardless of the HLA-B*57:01 prevalence in the ***,the US Food and Drug Administration(FDA) and international HIV treatment guidelines recommend a routine HLA-B*57:01 screening prior to abacavir treatment to decrease false positive diagnosis and prevent abacavir-induced *** studies of abacavir-induced HSR and the implementation of the HLA-B*57:01 screening in the clinic represent a successful example of the use of pharmacogenetics for personalized diagnosis and therapy.

关键词： personalized medicine pharmacogenetics drug safety abacavir hypersensitivity reaction (HSR) HLA-B*57:01 HLA-B*57-01 screening

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Introduction

Biomedical and Environmental Sciences 1991年第1期4卷 2-7页

作者： RONALD W.HART LOUIS W.CHANG ANGELO TURTURRO FRED F.KADLUBAR DHHS/PHS/FDA national center for toxicological research DHHS/PHS/FDA National Center for Toxicological ResearchDHHS/PHS/FDA National Center for Toxicological ResearchDHHS/PHS/FDA National Center for Toxicological Research Jefferson Arkansas 72079Jefferson Arkansas 72079Jefferson Arkansas 72079Jefferson Arkansas 72079

Over the past 30 years, there has been a general change of emphasis in toxicology from the traditional concerns with poisons and antidotes to understanding the chronic toxic effects associated with exposure to environmental agents. The major cause of this shift was a focusing of public interest on long-term health effects of man-made chemicals. This public awareness was motivated in part by the successes of public health sanitarians in controlling infectious diseases (with the recent exception of AIDS), which resulted in the lengthening of life expectancy in the population (Hart and Turturro, 1990). This change in emphasis has radically altered the scientific methods Used in toxicology. There are basic differences in evaluating short-term and long-term consequences of toxic exposure. Interestingly, techniques similar to those used to understand the effects of long-term toxicity are also useful in understanding aging (Hart and Turturro, 1988). Factors that contribute to these differences include the comp

关键词： awareness emphasis exposure motivated chemicals consequences evaluating Introduction altered toxicity

Critical role of bioinformatics in translating huge amounts of next-generation sequencing data into personalized medicine

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Science China(Life Sciences) 2013年第2期56卷 110-118页

作者： HONG HuiXiao ZHANG WenQian SHEN Jie SU ZhenQiang NING BaiTang HAN Tao PERKINS Roger SHI LeMing TONG WeiDa Division of Bioinformatics and Biostatistics National Center for Toxicological ResearchUS Food and Drug Administration Beijing Genomic Institute Beishan Industrial Zone Division of Systems Biology National Center for Toxicological ResearchUS Food and Drug Administration

Realizing personalized medicine requires integrating diverse data types with *** most vital data are genomic information for individuals that are from advanced next-generation sequencing(NGS) technologies at *** technologies continue to advance in terms of both decreasing cost and sequencing speed with concomitant increase in the amount and complexity of the *** prodigious data together with the requisite computational pipelines for data analysis and interpretation are stressors to IT infrastructure and the scientists conducting the work *** is increasingly becoming the rate-limiting step with numerous challenges to be overcome for translating NGS data for personalized *** review some key bioinformatics tasks,issues,and challenges in contexts of IT requirements,data quality,analysis tools and pipelines,and validation of biomarkers.

关键词： personalized medicine next-generation sequencing bioinformatics short reads alignment assemble data analysis

Biomarkers of Aging: An Overview

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Biomedical and Environmental Sciences 1991年第Z1期 130-133页

作者： ANGELO TURTURRO,RONALD W.HART national center for toxicological research Jefferson national center for toxicological research Jefferson Akansas 72079 Akansas 72079

关键词： Biomarkers of Aging An Overview

The Effects of Dietary Restriction and Aging on in Vivo and in Vitro Binding of Aflatoxin B1 to Cellular DNA

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Biomedical and Environmental Sciences 1991年第Z1期 134-143页

作者： MING W.CHOU,REX A.PEGRAM,PU GAO,S.R.HANSARD,J.G.SHADDOCK,D.A.CASCIANO national center for toxicological research Jefferson national center for toxicological research Jefferson national center for toxicological research Jefferson national center for toxicological research Jefferson national center for toxicological research Jefferson national Arkansas AR 72079 To whom repucsts for reprints should be addressed Arkansas AR 72079 US EPA HERL MD-74 research Triangle Park NC 27711 Arkansas AR 72079 Arkansas AR 72079 Arkansas AR 72079 center for toxicological research Jefferson Arkansas AR 72079

Laboratory animals maintained on a reduced calorie but nutritionally adequate diet have extended life spans and lowered incidences of spontaneous and chemically induced cancers compared to ad libitum- fed counterparts. Many of the effects of dietary restriction on laboratory animals have been suggested to be related to a deceleration of the aging process. The inhibition of age-related changes in xenobiotic metabolizing enzyme activities by dietary restriction has previously been reported. Alterations of these enzyme activities may cause changes in metabolic activation of carcinogens and, therefore, carcinogen-DNA binding. DNA-repair capability has also been reported to be enhanced in diet-restricted rats. Using AFB 1 as a model carcinogen, we have studied in vivo and in vitro hepatic AFB 1-DNA binding, demonstrating that dietary restriction (60% of ad libitum consumption) may decrease the metabolic activation of AFB1, and subsequently reduce AFBI-DNA binding. Our preliminary results obtained from the AF

关键词： The Effects of Dietary Restriction and Aging on in Vivo and in Vitro Binding of Aflatoxin B1 to Cellular DNA AFB

Development of the sexually dimorphic nucleus of the preoptic area and the influence of estrogen-like compounds

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Neural Regeneration research 2013年第29期8卷 2763-2774页

作者： Zhen He Sherry Ann Ferguson Li Cui Lazar John Greenfield Merle Gale Paule Division of Neurotoxicology National Center for Toxicological ResearchFood and Drug Administration Department of Neurology University of Arkansas for Medical Sciences

One of the well-defined sexually dimorphic structures in the brain is the sexually dimorphic nucleus, a cluster of cells located in the preoptic area of the hypothalamus. The rodent sexually dimorphic nucleus of the preoptic area can be delineated histologically using conventional Nissl staining or immunohistochemically using calbindin D28K immunoreactivity. There is increasing use of the cal- bindin D28K-delineated neural cluster to define the sexually dimorphic nucleus of the preoptic area in rodents. Several mechanisms are proposed to underlie the processes that contribute to the sexual dimorphism （size difference） of the sexually dimorphic nucleus of the preoptic area. Recent evidence indicates that stem cell activity, including proliferation and migration presumably from the 3^rd ventricle stem cell niche, may play a critical role in the postnatal development of the sexually dimorphic nucleus of the preoptic area and its distinguishing sexually dimorphic feature： a signifi-cantly larger volume in males. Sex hormones and estrogen-like compounds can affect the size of the sexually dimorphic nucleus of the preoptic area. Despite considerable research, it remains un-clear whether estrogen-like compounds and/or sex hormones increase size of the sexually dimor-phic nucleus of the preoptic area via an increase in stem cell activity originating from the 3^rd ventricle stern cell niche.

关键词： neural regeneration review sexual orientation sexual behavior calbindin D28K estrogen-likecompound bisphenol A neural stem cells grants-supported paper neuroregeneration

Could wastewater analysis be a useful tool for China?——A review

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Journal of Environmental Sciences 2015年第1期27卷 70-79页

作者： Jianfa Gao Jake O'Brien Foon Yin Lai Alexander L.N.van Nuijs Jun He Jochen F.Mueller Jingsha Xu Phong K.Thai Faculty of Science and Engineering University of Nottingham Ningbo China national research Centre for Environmental Toxicology The University of Queensland toxicological center University of Antwerp

Analysing wastewater samples is an innovative approach that overcomes many limitations of traditional surveys to identify and measure a range of chemicals that were consumed by or exposed to people living in a sewer catchment area. First conceptualised in 2001, much progress has been made to make wastewater analysis（WWA） a reliable and robust tool for measuring chemical consumption and/or exposure. At the moment, the most popular application of WWA, sometimes referred as sewage epidemiology, is to monitor the consumption of illicit drugs in communities around the globe, including China. The approach has been largely adopted by law enforcement agencies as a device to monitor the temporal and geographical patterns of drug consumption. In the future, the methodology can be extended to other chemicals including biomarkers of population health（e.g. environmental or oxidative stress biomarkers, lifestyle indicators or medications that are taken by different demographic groups） and pollutants that people are exposed to（e.g. polycyclic aromatic hydrocarbons,perfluorinated chemicals, and toxic pesticides）. The extension of WWA to a huge range of chemicals may give rise to a field called sewage chemical-information mining（SCIM） with unexplored potentials. China has many densely populated cities with thousands of sewage treatment plants which are favourable for applying WWA/SCIM in order to help relevant authorities gather information about illicit drug consumption and population health status. However, there are some prerequisites and uncertainties of the methodology that should be addressed for SCIM to reach its full potential in China.

关键词： Drug consumption Wastewater analysis Biomarkers Population health

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Introduction

Biomedical and Environmental Sciences 1991年第Z1期 2-7页

作者： RONALD W.HART,LOUIS W.CHANG,ANGELO TURTURRO,FRED F.KADLUBAR DHHS/PHS/FDA national center for toxicological research DHHS/PHS/FDA national center for toxicological research DHHS/PHS/FDA national center for toxicological research DHHS/PHS/FDA national center for toxicological research Jefferson Arkansas 72079 Jefferson Arkansas 72079 Jefferson Arkansas 72079 Jefferson Arkansas 72079

关键词： awareness emphasis exposure motivated chemicals consequences evaluating Introduction altered toxicity