Expression of adhesion receptors on rat limb bud cells and results of treatment with a thalidomide derivative.
The expression of several adhesion surface receptors was studied on cells of early limb bud development of 58 Wistar rats treated orally with two daily doses of the thalidomide derivative EM12 (2 x 50 mg/kg body weight) from day 7 to 10 of pregnancy. EM12 is a more potent teratogen than thalidomide. Limb bud cells of 56 untreated animals served as controls. The studies revealed that the integrins CD11a, CD11b, CD18, CD49d, and CD61, as well as the additional adhesion receptors CD54, CD62L, and the transferrin receptor CD71 were expressed on day 11 of gestation to various degrees on these embryonic cells. In contrast to results of previous studies with a non-human primate (Callithrix jacchus) there was no down-regulation of any of these receptors on the surface of limb bud cells of the rat embryos after treatment with EM12. This result is in accordance with the lack of teratogenicity in this rodent species.
Thiel
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R
Institute of Clinical Pharmacology and Toxicology, Department of Toxicology, Benjamin Franklin Medical Center, Freie Universität Berlin, Germany. r.thiel@medizin.fu-berlin.de
Kastner
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U
Neubert
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D000818:Animals; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D005260:Female; D016023:Integrins / Q000096:biosynthesis / Q000187:drug effects; D018878:Limb Buds / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D013723:Teratogens / Q000494:pharmacology*; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D016023:Integrins; D013723:Teratogens; C001079:2-(2,6-dioxopiperidin-3-yl)phthalimidine; D013792:Thalidomide