Discriminative power of an assay for automated in vitro screening of teratogens

Peter S Walmod; Ute Gravemann; Heinz Nau; Vladimir Berezin; Elisabeth Bock

doi:10.1016/j.tiv.2004.01.007

Discriminative power of an assay for automated in vitro screening of teratogens

Peter S Walmod, Ute Gravemann, Heinz Nau, Vladimir Berezin, Elisabeth Bock

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

16 Citationer (Scopus)

Abstract

Udgivelsesdato: 2004-Aug

Originalsprog	Engelsk
Tidsskrift	Toxicology in Vitro
Vol/bind	18
Udgave nummer	4
Sider (fra-til)	511-525
Antal sider	14
ISSN	0887-2333
DOI	https://doi.org/10.1016/j.tiv.2004.01.007
Status	Udgivet - 2004

Bibliografisk note

Keywords: Animals; Automation; Cell Culture Techniques; Cell Proliferation; Cell Shape; Embryonic Development; Fibroblasts; Mice; Sensitivity and Specificity; Teratogens; Toxicity Tests

Adgang til dokumentet

10.1016/j.tiv.2004.01.007

Citationsformater

@article{8c7871b074c311dbbee902004c4f4f50,

title = "Discriminative power of an assay for automated in vitro screening of teratogens",

abstract = "Screening for potential teratogenicity of 20 test compounds was performed using a computerised microscope workstation for determination of cytotoxicity, proliferation and morphology of fibroblastoid murine L929-cells. The test compounds, which were divided into four classes according to teratogenicity were: 5-bromo-2(')-deoxyuridine, 6-aminonicotinamide, acrylamide, boric acid, D-(+)-camphor, dimethadione, dimethyl phthalate, diphenhydramine, hydroxyurea, isobutyl-ethyl-valproic acid, lithium chloride, methyl mercury chloride, methotrexate, methoxyacetic acid, penicillin G, all-trans-retinoic acid, pentyl-4-yn-valproic acid, saccharin, salicylic acid and valproic acid. All compounds, with the exception of dimethadione inhibited proliferation in a linear dose-dependent manner, and there were statistically significant compound class-dependent differences between the IC(50)-values for the compounds (p<0.0374), the strongest teratogens being the most potent. Furthermore, the average efficacies (maximum relative change) for 10 parameters describing cell morphology exhibited statistically significant compound class-dependent differences (p<0.0001), the class I and II compounds exhibiting significantly lower efficacies than the class III and IV compounds (p<0.01). Thus, test compounds affected both the proliferation and morphology of L-cells in manner demonstrating a general relationship with the teratogenic potency of the compounds. However, the moderate teratogens dimethadione and lithium chloride only had minor effects on the morphology and proliferation of the cells whereas the non-teratogen diphenhydramine had effects on both proliferation and morphology comparable to the strong teratogens.",

author = "Walmod, {Peter S} and Ute Gravemann and Heinz Nau and Vladimir Berezin and Elisabeth Bock",

note = "Keywords: Animals; Automation; Cell Culture Techniques; Cell Proliferation; Cell Shape; Embryonic Development; Fibroblasts; Mice; Sensitivity and Specificity; Teratogens; Toxicity Tests",

year = "2004",

doi = "10.1016/j.tiv.2004.01.007",

language = "English",

volume = "18",

pages = "511--525",

journal = "Toxicology in Vitro",

issn = "0887-2333",

publisher = "Pergamon Press",

number = "4",

}

TY - JOUR

T1 - Discriminative power of an assay for automated in vitro screening of teratogens

AU - Walmod, Peter S

AU - Gravemann, Ute

AU - Nau, Heinz

AU - Berezin, Vladimir

AU - Bock, Elisabeth

N1 - Keywords: Animals; Automation; Cell Culture Techniques; Cell Proliferation; Cell Shape; Embryonic Development; Fibroblasts; Mice; Sensitivity and Specificity; Teratogens; Toxicity Tests

PY - 2004

Y1 - 2004

N2 - Screening for potential teratogenicity of 20 test compounds was performed using a computerised microscope workstation for determination of cytotoxicity, proliferation and morphology of fibroblastoid murine L929-cells. The test compounds, which were divided into four classes according to teratogenicity were: 5-bromo-2(')-deoxyuridine, 6-aminonicotinamide, acrylamide, boric acid, D-(+)-camphor, dimethadione, dimethyl phthalate, diphenhydramine, hydroxyurea, isobutyl-ethyl-valproic acid, lithium chloride, methyl mercury chloride, methotrexate, methoxyacetic acid, penicillin G, all-trans-retinoic acid, pentyl-4-yn-valproic acid, saccharin, salicylic acid and valproic acid. All compounds, with the exception of dimethadione inhibited proliferation in a linear dose-dependent manner, and there were statistically significant compound class-dependent differences between the IC(50)-values for the compounds (p<0.0374), the strongest teratogens being the most potent. Furthermore, the average efficacies (maximum relative change) for 10 parameters describing cell morphology exhibited statistically significant compound class-dependent differences (p<0.0001), the class I and II compounds exhibiting significantly lower efficacies than the class III and IV compounds (p<0.01). Thus, test compounds affected both the proliferation and morphology of L-cells in manner demonstrating a general relationship with the teratogenic potency of the compounds. However, the moderate teratogens dimethadione and lithium chloride only had minor effects on the morphology and proliferation of the cells whereas the non-teratogen diphenhydramine had effects on both proliferation and morphology comparable to the strong teratogens.

AB - Screening for potential teratogenicity of 20 test compounds was performed using a computerised microscope workstation for determination of cytotoxicity, proliferation and morphology of fibroblastoid murine L929-cells. The test compounds, which were divided into four classes according to teratogenicity were: 5-bromo-2(')-deoxyuridine, 6-aminonicotinamide, acrylamide, boric acid, D-(+)-camphor, dimethadione, dimethyl phthalate, diphenhydramine, hydroxyurea, isobutyl-ethyl-valproic acid, lithium chloride, methyl mercury chloride, methotrexate, methoxyacetic acid, penicillin G, all-trans-retinoic acid, pentyl-4-yn-valproic acid, saccharin, salicylic acid and valproic acid. All compounds, with the exception of dimethadione inhibited proliferation in a linear dose-dependent manner, and there were statistically significant compound class-dependent differences between the IC(50)-values for the compounds (p<0.0374), the strongest teratogens being the most potent. Furthermore, the average efficacies (maximum relative change) for 10 parameters describing cell morphology exhibited statistically significant compound class-dependent differences (p<0.0001), the class I and II compounds exhibiting significantly lower efficacies than the class III and IV compounds (p<0.01). Thus, test compounds affected both the proliferation and morphology of L-cells in manner demonstrating a general relationship with the teratogenic potency of the compounds. However, the moderate teratogens dimethadione and lithium chloride only had minor effects on the morphology and proliferation of the cells whereas the non-teratogen diphenhydramine had effects on both proliferation and morphology comparable to the strong teratogens.

U2 - 10.1016/j.tiv.2004.01.007

DO - 10.1016/j.tiv.2004.01.007

M3 - Journal article

C2 - 15130609

SN - 0887-2333

VL - 18

SP - 511

EP - 525

JO - Toxicology in Vitro

JF - Toxicology in Vitro

IS - 4

ER -