ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)2:3/4<221::AID-TCM1770020304>3.0.CO;2-7

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractRodent embryos can be grown in vitro during a period of rapid organogenesis. During a 24–48 hour culture period, growth and development closely approximate the values of embryos in utero at the same gestational stage. Embryos can be exposed to carefully controlled concentrations of test substances in a system which is free of maternal variables such as nutritional status or stress effects. Developmental abnormalities are limited to those systems developing during the culture period, but those available may show heightened sensitivity relative to the embryo in utero.Recently several systems have been developed which permit incorporation of either metabolites or metabolic enzymes in embryo culture. These materials can be obtained from species other than that of the test embryos. Because studies have shown the importance of maternal metabolism in the activation and inactivation of teratogens, it is hoped that these systems will enable us to understand the biochemical basis of species variability in teratogenic sensitivity and construct a teratogen screen which can reliably identify compounds which pose teratogenic hazards to human

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)2:3/4<231::AID-TCM1770020305>3.0.CO;2-1

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractHead‐fold and early somite stages of mouse and rat embryos maintained in wholeembryo culture throughout much of the period of organogenesis demonstate normal growth and morphogenesis. Embryos directly exposed to teratogens in the culture system and embryos cultured in serum from adult animals treated with toxic compounds develop congenital abnormalities that resemble malformations induced in vivo by these same agents. Furthermore, the defects are dose‐ and stage‐dependent, such that higher doses produce a greater percentage of malformed embryos, and younger embryos are more susceptible than older ones. These results‐together with the observations that 1) data are rapidly produced, 2) quantifiable endpoints can be measured in mammalian systems at costs considerably below those inherent in in vivo analyses, and 3) the potential exists for monitoring serum toxicity in humans and primates — suggest that the whole‐embryo culture system may be useful as a screening technique for potentially teratogenic

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)2:3/4<243::AID-TCM1770020306>3.0.CO;2-U

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractIn vitro systems afford a unique opportunity for investigating the direct interaction of substances with developing morphogenetic systems (MGSs), since maternal influences are excluded. As a carrier of a complete set of MGSs, the chick embryo in ovo manifests an advantage over those in vitro systems that employ isolated embryos or embryonic tissues that have only limited survival. Under controlled experimental conditions including standardization of subjects, administration technique and mode of evaluation according to the basic principles of teratology, the chick embryo test was demonstrated to be reliable and to afford quantifiable endpoints for evaluation (e.g., specific embryotoxicity effect level, positive dose response, and a stage response and effect). Individual compounds, mixtures of compounds, and even poorly identified extracts can easily be tested. The chick embryo possesses its own basic enzyme‐catalyzed drug‐transformation capacity and, moreover, it can be used for screening specific human metabolites. Comparative studies have indicated a high predictive value of the chick embryo system relative to other in vitro systems as well as to whole‐animal te

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)2:3/4<255::AID-TCM1770020307>3.0.CO;2-M

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractBy a uniformly applied protocol, adult hydra are exposed to a test substance over a broad range of concentrations, and the minimal toxic concentration is determined to within one‐tenth log. In a second experiment, dissociated hydra cells are manipulated into a configuration wherein, if undisturbed, they will achieve the developmental events characteristic of any embryo and undergo total whole‐body regeneration. During its 4‐day ontogenesis this artificial “embryo” is exposed to the test substance by the same protocol as the adult and the minimal developmentally toxic concentration is determined to within one‐tenth log. The ratio of the adult (A) to the developmentally (D) toxic concentration is calculated. A small A/D ratio indicates that the substance disrupts development only at or near the concentration also toxic to the adult (a developmentally nonhazardous substance or coeffective teratogen). A large A/D ratio indicates that a substance disrupts developmental events at a small fraction of the exposure toxic to adults (a developmental hazard). The system is directly predictable of a putative teratogen's hazard potential (A/D ratio) in standard laboratory animals and man. It provides an objective and reliable means to prioritize otherwise untested substances according to the need for further study of their development

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)2:3/4<263::AID-TCM1770020308>3.0.CO;2-I

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractFree‐living flatworms such as planarians are inexpensive to culture, maintain, and use for toxicologic testing in the laboratory. A considerable number of basic studies by ourselves and others indicate that, in simplified miniature, they possess many features of biochemical and physiologic organization similar to higher animals such as mammals. These include a well‐developed brain with a varied behavioral repertoire including complex maneuvers of prey capture and learning, with a number of the same neurotransmitters used in mammalian brain. They are sensitive to a variety of the same toxicants. Undifferentiated totipotent stem cells, i.e., “neoblasts,” which are capable of mitosis and differentiation into any of the various specialized cell types, permit regeneration of complete planarians from fragments. They also provide new cells to replace those lost in the normal cellular turn‐over of nonregenerating planarians. Both regeneration of surgical fragments and aberrant remodeling of whole planarians model important features of embyrogenesis and are potentially useful for assaying teratogens. Results are described from studies in which various representative teratogenic toxicants were tested in these two different planarian paradigms. The potential of planarian cephalic regeneration for behavioral teratogenesis investigations is also

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)2:3/4<277::AID-TCM1770020309>3.0.CO;2-8

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractDrosophila melanogasteris being investigated for its potential to aid in identifying priority chemicals for teratologic study. The method encompasses treating larvae over the entire metamorphosis period, i.e., from the egg through three instar stages to pupa formation, by incorporating the test chemical into the medium. Adult flies are systematically examined under a binocular microscope for external morphological anomalies. Data from treated flies can be compared with those from concurrent control flies using standard statistical tests. Results from this developmental work reveal a dramatic and reproducible response ofDrosophilato various chemical treatments. Validation studies, testing known teratogens and nonteratogens, are necesary before such a system can be incorporated into existing teratologic screening regimens.

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)2:3/4<293::AID-TCM1770020310>3.0.CO;2-W

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractThe limb bud organ culture system offers a variety of endpoints which may be monitored in the screening process. These are: cell proliferation, differential growth, morphogenetic cell death, size and shape of limb parts, chondrogenesis, collagen or proteoglycan biosynthesis, etc. Essentials of the system including various parameters of normal limb bud development in vitro are described. These parameters serve to gauge the effects of test chemicals with unknown hazard potential. Validation has been carried out only to a limited extent. Further, it needs to be combined with an efficient drug metabolizing preparation before it can achieve its full potential as a short‐term screening syste

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)2:3/4<303::AID-TCM1770020311>3.0.CO;2-I

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractMesenchymal cells from the prefusion human embryonic palate have been established in culture and can be grown in either a serum‐free hormone‐supplemented medium or a serum‐containing medium. The growth of these cells is quite rapid in culture and inhibited in a dose‐dependent manner by most teratogens thus far tested, such as dexamethasone. These cells are highly sensitive to a variety of DNA synthetic and mitotic inhibitors. The responses of these cells are complementary to the ovarian tumor cell attachment assay of Braun et al [1, and in this volume]. When used in conjunction with the tumor cells, the overall reliability is greater than 90% with only one false‐negative, al

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)2:3/4<313::AID-TCM1770020312>3.0.CO;2-C

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractWe have tested the effects of teratogenic and nonteratogenic compounds on cultures of differentiating embryonic neural crest cells. Compounds were evaluated for their effects on the growth or differentiation of the cells based on morphologic criteria or on quantitative changes in biochemical markers for the differentiated cells. When metabolic activation may be required, compounds were incubated in the cultures in the presence of the postmitochondrial supernatant fraction of rat liver microsomes. Nine of 11 compounds with proven teratogenic effects in vivo induced readily detectable morphologic changes in differentiating cultures. In contrast, none of the nonteratogenic compounds tested had an effect on these cultures. The use of differentiating cell cultures as a screening system for teratogens is discussed.

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)2:3/4<319::AID-TCM1770020313>3.0.CO;2-3

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY