Cell transformation by chemical agents--a review and analysis of the literature. A report of the U.S. Environmental Protection Agency Gene-Tox Program

The literature on cell transformation by chemical carcinogens has been critically reviewed. This subject is highly relevant to carcinogenesis in vivo, because the phenotypic changes that are collectively referred to as cell transformation usually involve the acquisition of tumorigenicity on inoculation into suitable rodent hosts. The systems chosen for review fall into 3 categories: cell strains (cells with a limited lifespan); cell lines (cells with an unlimited lifespan); and oncogenic viral-chemical interactions involving cells (Fischer rat embryo cells expressing an endogenous retrovirus, mouse embryo cells expressing the AKR leukemia virus, chemical enhancement of a simian adenovirus, SA7 transformation of Syrian hamster or rat embryo cells). Of the entire literature reviewed, 117 papers have been accepted for data abstraction by pre-defined criteria; these include 41 references to cell strains, 40 in cell lines, and 38 in viral-chemical interactions including cells. Because different systems have been reviewed, it would be meaningless to group all the compounds. The overall summary of the systems is as follows (many compounds have been tested in more than one system and, hence, are duplicated in these totals). (Chart: see text) In general, there is a reasonably good correlation between the results of the cell transformation systems and in vivo carcinogenesis. However, the many deficiencies of the EPA Merged Carcinogen List preclude definitive comparisons. Moreover, a number of 'false negatives' were obtained in systems that did not employ external metabolic activation. Further validation of all systems is required, but it seems very probable that several cell transformation systems will become valuable in assaying (with reasonable time and cost) the carcinogenic potential of environmental chemicals.     

Studies on the Growth in Culture of Plant Cells: XII. A VERSATILE SYSTEM FOR THE LARGE SCALE BATCH OR CONTINUOUS CULTURE OF PLANT CELL SUSPENSIONS

A versatile large-scale batch culture unit has been developedfor the growth of plant cell suspension cultures. This unithas been modified to permit of intermittent or continuous renewalof culture medium and, in a modified form, incorporated intoopen continuous culture systems of the chemostat and turbidostattype. A fully automatic culture sampler has been incorporatedinto the basic culture unit. The culture systems described havebeen successfully operated using a cell suspension derived fromAcer pseudoplatanus and results are presented demonstratingsynchronous growth in batch culture, prolonged logarithmic increassein cell number under conditions of high aeration and culturemedium renewal, and steady states of growth resulting from automaticregulation of the optical density of the cell suspension andfrom fixed rates of displacement of cell suspension by new medium.The potentialities of the culture systems are discussed in thelight of the experimental results presented.     

Responsive systems for cell sheet detachment

Cell sheet engineering has been progressing rapidly during the past few years and has emerged as a novel approach for cell based therapy. Cell sheet harvest technology enables fabrication of viable, transplantable cell sheets for various tissue engineering applications. Currently, the majority of cell sheet studies use thermo-responsive systems for cell sheet detachment. However, other responsive systems began showing their potentials for cell sheet harvest. This review provides an overview of current techniques in creating cell sheets using different types of responsive systems including thermo-responsive, electro-responsive, photo-responsive, pH-responsive and magnetic systems. Their mechanism, approach, as well as applications for cell detachment have been introduced. Further development of these responsive systems will allow efficient cell sheet harvesting and patterning of cells to reconstruct complex tissue for broad clinical applications.     

VicRK(YycFG)双组分调节系统

细菌双组分调节系统,或称之为双组分信号转导系统,是细菌感应外界多变环境,维持自身存活和生长繁衍的重要感应系统.在这些调节系统中,最早发现于枯草芽孢杆菌的VicRK(YycFG)系统因与细胞存活密切相关而倍受关注.该系统存在于少数低G+C含量的革兰氏阳性菌中,包括金黄色葡萄球菌和肺炎链球菌等致病菌,高度保守.许多证据显示,VicRK(YycFG)具有调控细胞壁合成与代谢、胞膜完整、细胞分裂、脂类代谢、多糖合成与被膜形成以及细菌毒力等多种功能,参与细胞的生长、分裂与感染.该系统异常可导致细菌生活力严重下降,甚至死亡,因而成为防治该类病原菌的重要靶标.     

Algorithms for optimization of the transport system in living and artificial cells

An optimization of the transport system in a cell has been considered from the viewpoint of the operations research. Algorithms for an optimization of the transport system of a cell in terms of both the efficiency and a weak sensitivity of a cell to environmental changes have been proposed. The switching of various systems of transport is considered as the mechanism of weak sensitivity of a cell to changes in environment. The use of the algorithms for an optimization of a cardiac cell has been considered by way of example. We received theoretically for a cell of a cardiac muscle that at the increase of potassium concentration in the environment switching of transport systems for this ion takes place. This conclusion qualitatively coincides with experiments. The problem of synthesizing an optimal system in an artificial cell has been stated.     

Acetate addition to an immobilized yeast column of ethanol production

Acetate, a by-product of ethanol fermentation by Saccharomyces cerevisiae, has been shown to inhibit cell growth if present in high concentrations. Consequently, acetate has been considered undesirable in systems where the production rate depends upon steady-state growth. Acetate, however, may be desirable in some systems since it increases the specific rate of ethanol production by increasing the maintenance requirements of yeast. In immobilized cell reactors using the crosslinking method, steady state is not achieved and cell overgrowth is a problem. This article presents the results of a study aimed at taking advantage of the use of acetate, both to reduce cell overgrowth and to increase productivity. Various concentrations of acetate were added to batch and plug flow systems, while monitoring the effects on cell growth and ethanol production. The productivity was increased by as much as 50% in an immobilized cell reactor (ICR), while cell growth was greatly reduced.     

Toxin-antitoxin systems influence biofilm and persister cell formation and the general stress response

In many genomes, toxin-antitoxin (TA) systems have been identified; however, their role in cell physiology has been unclear. Here we examine the evidence that TA systems are involved in biofilm formation and persister cell formation and that these systems may be important regulators of the switch from the planktonic to the biofilm lifestyle as a stress response by their control of secondary messenger 3',5'-cyclic diguanylic acid. Specifically, upon stress, the sequence-specific mRNA interferases MqsR and MazF mediate cell survival. In addition, we propose that TA systems are not redundant, as they may have developed to respond to specific stresses.     

Recombinant DNA approaches for the development of metabolic systems used in in vitro toxicology.

In the past few years there has been considerable progress in the development of mammalian cell systems for use in genetic toxicology by the stable transfer of genes/cDNAs coding for drug metabolizing enzymes directly into the target cell. Alternative approaches have also been developed in which mammalian cells are transiently transfected with cDNAs coding for drug-metabolizing enzymes and S9 preparations expressing a single metabolizing enzyme isolated and used for metabolic activation. Progress in these areas is reviewed here and the relative merits of the different approaches are discussed. Work to date has focused primarily on the cytochrome P450 family of enzymes, although other enzyme systems involved in xenobiotic metabolism have been used. The central theme of this review is the transfer of genetic information to improve the metabolic capability of cell systems used in genetic toxicology. However, a basic philosophy of the review is that genetic manipulation of cultured mammalian cells has the potential for developing systems to be used to better understand chemically induced toxicological effects.     

A simple correlation for predicting effective diffusivities in immobilized cell systems

A simple correlation method has been developed to predict effective diffusivities of small molecules in heterogeneous materials such as immobilized cell systems. This correlation uses a single diffusivity measurement at one cell volume fraction to predict diffusivities for any other volume fraction of cell. The method has been applied to 20 sets of published diffusivity measurements in immobilized cell systems and accurately predicts affective diffusivities of molecules for the full range of cell fractions. It may also be used to predict effective diffusivities in heterogeneous materials in which the diffusivity of a molecule in each phase and the volume fraction of each phase are known. (c) 1996 John Wiley & Sons, Inc.     

Plant cell cultures for the production of recombinant proteins

The use of whole plants for the synthesis of recombinant proteins has received a great deal of attention recently because of advantages in economy, scalability and safety compared with traditional microbial and mammalian production systems. However, production systems that use whole plants lack several of the intrinsic benefits of cultured cells, including the precise control over growth conditions, batch-to-batch product consistency, a high level of containment and the ability to produce recombinant proteins in compliance with good manufacturing practice. Plant cell cultures combine the merits of whole-plant systems with those of microbial and animal cell cultures, and already have an established track record for the production of valuable therapeutic secondary metabolites. Although no recombinant proteins have yet been produced commercially using plant cell cultures, there have been many proof-of-principle studies and several companies are investigating the commercial feasibility of such production systems.     

Multifunctional plasma membrane redox systems

All the biological membranes contain oxidoreduction systems actively involved in their bioenergetics. Plasma membrane redox systems seem to be ubiquitous and they have been related to several important functions, including not only their role in cell bioenergetics, but also in cell defense through the generation of reactive oxygen species, in iron uptake, in the control of cell growth and proliferation and in signal transduction. In the last few years, an increasing number of mechanistic and molecular studies have deeply widened our knowledge on the function of these plasma membrane redox systems. The aim of this review is to summarize what is currently known about the components and physiological roles of these systems.     

Evolutionarily conserved concepts in glial cell biology

The evolutionary conservation of glial cells has been appreciated since Ramon y Cajal and Del Rio Hortega first described the morphological features of cells in the nervous system. We now appreciate that glial cells have essential roles throughout life in most nervous systems. The field of glial cell biology has grown exponentially in the last ten years. This new wealth of knowledge has been aided by seminal findings in non-mammalian model systems. Ultimately, such concepts help us to understand glia in mammalian nervous systems. Rather than summarizing the field of glial biology, I will first briefly introduce glia in non-mammalian models systems. Then, highlight seminal findings across the glial field that utilized non-mammalian model systems to advance our understanding of the mammalian nervous system. Finally, I will call attention to some recent findings that introduce new questions about glial cell biology that will be investigated for years to come.     

HCV复制子与细胞培养体系研究进展

丙型肝炎是由丙型肝炎病毒(hepatitis C virus,HCV)感染所导致的传染性肝病,呈现世界性流行态势,严重危害人类健康。由于病毒自身高度突变,以及广泛高效的细胞培养体系和合适的小动物模型缺乏,目前尚无可有效预防的疫苗。自1989年丙型肝炎病毒基因组首次被确定以来,Con1(1b)亚基因组复制子和JFH1(2a)毒株细胞培养体系相继建立。以此为工具,HCV生活周期多个关键环节得以阐明。近年来,研究者在Con1亚基因组复制子、JFH1和J6/JFH1细胞培养体系的基础上,构建出多个基因型和亚型的复制子和细胞培养体系。不同的体系在HCV复制与致病机制研究、抗病毒药物筛选方面,具有不同的用途及优缺点。针对HCV复制子与细胞培养体系的研究进展进行综述,可为HCV的相关研究提供参考。     

Partitioning of host and recombinant cells in aqueous two-phase polymer systems

The separation of host and recombinant Escherichia coli bacterial cells has been studied using the surface-sensitive technique of partitioning in aqueous two-phase polymer systems. Experiments were designed to probe charge-and hydrophobicity-related property differences of antibiotic-resistant recombinant cells and their antibiotic-sensitive hosts. Differential partitioning was observed in both charge-sensitive and non-charge-sensitive phase systems for three host-recombinant cell systems, but the non-charge-related effects appear to have a greater impact on partitioning behavior. This result suggests that plasmid-encoded products related to antibiotic resistance modify the surface hydrophobicity of the E. coli bacterial cell and that these differences can be exploited for cell separation.     

Cell surface carbohydrates in cell adhesion.

Carbohydrates are ubiquitous constituents of cell surfaces, and possess many characteristics that make them ideal candidates for recognition molecules. In many systems where cell adhesion plays a critical role, carbohydrate binding proteins have been shown to bind to cell surface carbohydrates and participate in cell-cell interactions. Such systems include fertilization, development, pathogen-host recognition and inflammation. In particular the recent discovery of the LEC-CAMs and their importance in leukocyte biology has refocused attention on lectin-mediated cell adhesion. The LEC-CAMs offer good targets for the development of therapeutics based on carbohydrate structures.     

On the merits of viable-cell immobilisation

Many advantages have been claimed over the years for the use of immobilised cells, both as enzyme systems and as whole viable cell systems for complete fermentation reactions. However, few of the claims have been fully substantiated, and may not even be entirely justified. Most research is involved with single applications and the best that can be hoped for is some evidence that immobilised cells in each of these individual cases display some advantage over the equivalent free cell system. The purpose of this review is to assess the merits of viable cell immobilisation in the light of published literature and to elucidate the underlying mechanisms. Particular attention is paid to the generally unanticipated, but widely observed enhanced stability of immobilised cell fermentation processes.     

Mechanisms of the bactericidal action of hydrogen peroxide

The comparative study of some aspects of the bactericidal action of H2O2 on Escherichia coli, Staphylococcus aureus and Bacterium subtilis wild-type cells and their mutants with lesions in the systems of the reparation of DNA has been carried out. Hydrogen peroxide has been shown to cause disturbances in the structure and permeability of the cell wall, the cytoplasmic membrane, as well as to induce ribosomal lesions and the ruptures of bacterial DNA. The activity of the systems responsible for the reparation of lesions in the cell genome plays an important role in the resistance of bacteria to H2O2.     

Extracellular and immunological actions of zinc

Zinc is an essential trace element for the immune system, but also very important in other organ systems. Every highly proliferating cell system is dependent on sufficient availability of zinc. During the last decades the influence of zinc on various cell systems have been investigated. Multiple effects of exogenously added zinc have been described in in vitro culture systems and in in vivo systems. However, most of these effects are so far poorly understood, and the dosages used in the in vitro systems are not comparable and sometimes unphysiologically high. Especially in the immune system a number of effects were described and over the last ten years we have come to understand some molecular mechanisms of zinc in this cell system. A zinc deficiency is accompanied by an immunodeficiency, resulting in an increased number of infections. However, the immune function is delicately regulated by zinc, since both increased and decreased zinc levels result in a disturbed immune function. Therefore, zinc supplementation must be accurately supervised. In this review, we discuss the activity of extracellular zinc in four sections. 1. The effect of zinc on different in vitro cell systems, including keratinocytes, osteocytes and leukocytes, and the concentrations of zinc needed for a specific cell response. 2. The modulation of the innate immune system in vitro and in vivo. 3. The role of zinc in the B cell response and antibody production. 4. Effects of zinc on the development and function of T cells.     

Cell kinetics and longitudinal bone growth in birds

The theory that links cell division in epiphyseal cartilage plates to overall growth of long bones has been extended from linear growth systems to those in which proliferating and hypertrophied cells are not arranged in columns. Consideration has also been given to the analysis of non-parallel growth systems. The theory is illustrated by examples from the growth of chicken bones.     

Operation and pressure distribution of immobilized cell hollow fiber bioreactors

It has been cited in the literature on hollow fiber systems that pressure gradients persist, and the transmembrane flux of the hollow fiber system is dependent on the pattern of the pressure gradients. The pattern can be used to its advantage in immobilized enzyme systems. However, with immobilized living cell systems, the pressure gradients lead to a nonuniform environment within the hollow fiber cartridge and not necessarily favorable results. This article provides pertinent pressure-drop data on hollow fiber cartridges which are in flow configurations typical of immobilized cell culture work. The results illuminate operational problems that may arise in the culture of either anchorage dependent or independent cells. Possible solutions with crossflow systems are suggested.