The role of inhibited cell-cell communication in teratogenesis

Trosko, James E.; Chang, Chia‐Cheng; Netzloff, Michael L.

doi:10.1002/1520-6866(1990)2:1<31::aid-tcm1770020105>3.0.co;2-2

Cited by 69 publications

(22 citation statements)

References 106 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Trosko et al (13) proposed a hypothesis that teratogenesis and tumor promotion may share for this idea is lent by teratology studies which found that exposure to EGME and EGEE significantly lengthened gestation in rats and mice (22,23). Since labor is dependent upon the formation of gap junctions between the myometrial cells (4), increased length of parturition might be a sign of gap junction interference.…”

Section: Discussionmentioning

confidence: 99%

“…Pools of small metabolites (1000 to 1500 daltons, depending upon configuration) are also shared among cells joined by gap junctions (2 This assay has been widely applied to identify tumor promoters (11,12) and was recently proposed as an assay for teratogens (13). The assay was employed in the present study of ethylene glycol (EG) and some structurally related monoalkyl glycol ethers since some of these compounds have recently been found to be teratogenic in laboratory animals (14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Interruption of cell-cell communication in Chinese hamster V79 cells by various alkyl glycol ethers: implications for teratogenicity.

Loch‐Caruso¹,

Trosko²,

Corcos³

1984

Environ Health Perspect

View full text Add to dashboard Cite

Intercellular communication most likely plays a significant coordinating role in morphogenesis. Blockage of a specific type of intercellular communication, that mediated by gap junctions, has been proposed as a mechanism of action of some teratogens. Several glycol ethers have recently been shown to be teratogenic in laboratory animals. Because these compounds are negative in genotoxic assays, it is suggested that they may act by nongenetic, perhaps membrane-mediated mechanisms.In the present study several structurally related alkyl glycol ethers were examined for their ability to block junction-mediated intercellular communication. Interruption of intercellular communication was measured in vitro by an assay that depends on the transfer of metabolites via gap junctions, i.e., metabolic cooperation. All compounds tested-ethylene glycol (EG), ethylene glycol monomethyl ether (EGME), ethylene glycol monoethyl ether (EGEE), ethylene glycol monopropyl ether (EGPE), and ethylene glycol monobutyl ether (EGBE)-were able to block metabolic cooperation in vitro. The potencies of the compounds were inversely related to the length of the aliphatic chain, the dose required for maximum blockage increasing as the aliphatic chain shortened. Some differences in the maximum amount of blockage were detected, but these were not consistent and hence were not considered significant. Cytotoxicity, as measured by cell survival, was also related to the structure of the compound, generally increasing with increased length of the aliphatic chain. There were structurally related differences in the concentration ranges over which the compounds were effective. The noncytotoxic ranges over which communication was blocked became reduced as the length of the aliphatic chain increased. EG was effective over the broadest range, followed by EGME. The remaining compounds had very narrow effective ranges relative to EG and EGME. Because they are effective over such broad noncytotoxic ranges, blockage of intercellular communication may be most significant as a teratogenic mechanism for EG and EGME. Although the other compounds in the series also blocked communication, they were more cytotoxic and they interrupted communication in a relatively narrow window of concentrations. Consequently, interrupted intercellular communication may be mixed with cytotoxicity in the embryo and the mother, and thus be less specific as a mechanism of teratogenesis for EGEE, EGPE and EGBE.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Interruption of cell-cell communication in Chinese hamster V79 cells by various alkyl glycol ethers: implications for teratogenicity.

Loch‐Caruso¹,

Trosko²,

Corcos³

1984

Environ Health Perspect

View full text Add to dashboard Cite

show abstract

“…There appears to be a link between teratogenicity and carcinogenesis, in that many carcinogenic compounds are also teratogenic in nature, whereas teratogenic compounds are not necessarily implied to be carcinogenic (Trosko et al, 1982). The compounds which stimulate GJIC, such as retinoic acid and vitamin D, can also suppress tumour formation (Tanmahasamut and Sidell, 2005).…”

Section: The Relation Between Gap Junction Intercellular Communicatiomentioning

confidence: 99%

Structure and function of gap junction proteins: role of gap junction proteins in embryonic heart development

Ahir¹,

Pratten²

2014

Int. J. Dev. Biol.

View full text Add to dashboard Cite

Intercellular (cell-to-cell) communication is a crucial and complex mechanism during embryonic heart development. In the cardiovascular system, the beating of the heart is a dynamic and key regulatory process, which is functionally regulated by the coordinated spread of electrical activity through heart muscle cells. Heart tissues are composed of individual cells, each bearing specialized cell surface membrane structures called gap junctions that permit the intercellular exchange of ions and low molecular weight molecules. Gap junction channels are essential in normal heart function and they assist in the mediated spread of electrical impulses that stimulate synchronized contraction (via an electrical syncytium) of cardiac tissues. This present review describes the current knowledge of gap junction biology. In the first part, we summarise some relevant biochemical and physiological properties of gap junction proteins, including their structure and function. In the second part, we review the current evidence demonstrating the role of gap junction proteins in embryonic development with particular reference to those involved in embryonic heart development. Genetics and transgenic animal studies of gap junction protein function in embryonic heart development are considered and the alteration/disruption of gap junction intercellular communication which may lead to abnormal heart development is also discussed.

show abstract

“…Trosko and co-workers (7) found that a variety of chemicals have the ability to increase the recovery of mutant 6-TGr cells when co-cultured with wild-type 6 24 hr, at which time the medium is replaced with or without the test compound. The HEPM cells are then maintained in culture for an additional 72 hr.…”

Section: Critical Reviewmentioning

confidence: 99%

Teratological Research Using In Vitro Systems. IV. Cells in Culture

Welsh¹

1987

Environmental Health Perspectives

View full text Add to dashboard Cite

Several in vitro cellular systems designed to screen agents for teratogenic potential are described in this report. These assays were selected from a review of literature published through the spring of 1986 that generated over 100 references on teratological research using cell-based systems. Some of the assays have a broader application than others, but most require confirmation by one or more additional complementary tests because of the specificity of the teratogenic mechanism the assays are investigating. Included are systems that use analysis of tumor cell attachment; intercellular communication; growth of human embryonic palatal mesenchyme cells; progesterone production in porcine granulosa cells; differentiation of embryonic neural crest, limb bud, midbrain, and Drosophila cells; and differentiation of tumor cells. Because of the dynamic nature of cell culture work, the group of assays listed here should not be viewed as encompassing all cell systems of value with regard to teratogenicity testing; instead, the list represents several of the more prominent systems now being evaluated by the scientific community. Inhibition of Tumor Cell Attachment to Concanavalin A-Coated Surfaces IntroductionInteractions between embryonic cells have long been thought to be critical factors in embryonic development. The breakdown of these intracellular communications by physical intervention or genetic defects are thought to be associated with developmental anomalies. Braun and associates (1) have described an in vitro cell-to-surface recognition system using mouse ascites tumor cells to screen for potential teratogens. The use of tumor cells in this type of assay has several advantages: tumor cells are readily available, homogeneous, easy to prepare, and share many characteristics with embryonic cells. One characteristic that transformed fibroblasts, tumor cells, and some embryonic cells share is the ability to attach themselves to lectin-coated plastic surfaces, whereas normal fibroblasts attach poorly. This difference has been exploited as a means of differentiating chemicals that alter cell-surface interactions from those that do not. Tumor cells have been shown to attach rapidly and irreversibly to lectin-coated plastic disks because of interactions between carbohydrate moieties on the cell membrane and lectin receptors on the plastic sur (1,3,4). Another measure used to assess an agent's effect is the concentration required in order to inhibit attachment by 50% (ID50). Critical ReviewAttempts have been made to validate this system with over 100 chemicals in two basic categories, drugs and pesticides. The lowest effective dose reported for a teratogen was used to estimate teratogenic potency; in considering nonteratogens, the highest reported nonteratogenic dose was used. Inhibitory agents included anti-inflammatory drugs, sedatives, estrogens, antibiotics, organophosphates, chlorophenols, chlorinated hydrocarbons, and chlorinated cyclodienes. Braun and associates (3) observed 14 false negatives on testing 74 chemic...

show abstract

The role of inhibited cell-cell communication in teratogenesis

Cited by 69 publications

References 106 publications

Interruption of cell-cell communication in Chinese hamster V79 cells by various alkyl glycol ethers: implications for teratogenicity.

Interruption of cell-cell communication in Chinese hamster V79 cells by various alkyl glycol ethers: implications for teratogenicity.

Structure and function of gap junction proteins: role of gap junction proteins in embryonic heart development

Teratological Research Using In Vitro Systems. IV. Cells in Culture

Contact Info

Product

Resources

About