BINDING OF THALIDOMIDE BY MACROMOLECULES IN THE FETAL AND MATERNAL RAT

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 161; no. 2; pp. 348 - 360
• Main Authors: Bakay, B, Nyhan, W L
• Format: Journal Article
• Language: English
• Published: United States American Society for Pharmacology and Experimental Therapeutics 01.06.1968
• Subjects: Amino Acids - analysis; Animals; Carbon Isotopes; Cell Nucleus - analysis; Chromatography, Gel; DNA - analysis; DNA - metabolism; Electrophoresis; Female; Fetus - metabolism; Histones - analysis; Liver - cytology; Liver - embryology; Liver Extracts - metabolism; Macromolecular Substances - metabolism; Pregnancy; Pregnancy, Animal; Protein Binding; Proteins - metabolism; Rats; Receptors, Drug; RNA - analysis; RNA - metabolism; Thalidomide - metabolism; Ultracentrifugation
• ISSN: 0022-3565; 1521-0103

Cellular components of fetuses, maternal liver and plasma of pregnant rats were isolated 4 hr after the administration of C 14 -labeled thalidomide and examined for differences in composition and in the distribution of isotope. Subfractionation of the soluble macromolecules by zonal column electrophoresis revealed notable differences betweeen the composition of extracts of fetus and maternal liver. The fetus had considerably less near-neutral h proteins and substantially more highly acidic proteins. In this respect, the fetus resembled rapidly growing azo dye-induced hepatomas. In the fetus, thalidomide metabolites appeared to be bound specifically by the B class of highly acidic proteins. In contrast, in the liver, labeled metabolites were bound by all types of acidic and near-neutral proteins, including h 2 proteins. In the blood plasma most of the isotope was bound by albumin. Strongly and weakly bound thalidomide metabolites were found in the nucleohistones and acidic proteins of both fetus and liver. Little, if any, thalidomide or metabolites were found in the protein-free deoxyribonucleic acid and ribonucleic acid. Only trace amounts of strongly bound labeled metabolites were present in the microsomes of the fetus. In contrast, the microsomes of maternal liver contained a measurable amount of strongly bound radioactive products. The binding of thalidomide by the macromolecules of fetuses of rats differed markedly from the binding of chemical carcinogens by macromolecules of the target organ of susceptible animals.