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Biochemical Aspects of Teratology

1971; Elsevier BV; Linguagem: Inglês

10.1016/b978-0-08-017571-3.50036-x

Diether Neubert, H. J. Merker, E. Köhler, Ralf Krowke, H.-J. Barrach,

Science, Research, and Medicine

Mammalian embryonic tissue shows a special degree of sensitivity to the action of a variety of drugs as well as to environmental and nutritional factors when compared with the response of most tissues of an adult organism. This may lead to embryotoxic or teratogenic effects. Besides genetic defects acquired by the parental germ cells biochemical peculiarities - in which embryonic cells at certain stages of development deviate from cells of an adult organism - represent a prerequisite for an embryotoxic or teratogenic action. In order to get at least some understanding of the mode of action of embryotoxic effects, it is necessary to study the biochemistry of mammalian embryonic cells and the response of different embryonic cells to environmental factors or to drugs. Up to now very little is known of such peculiarities of mammalian embryonic tissue, quite in contrast to the numerous studies that have been performed on embryonic tissues from amphibia or from birds. Studies performed on such organisms are of great significance for developmental biology. But since we know that mammalian metabolism deviates quite considerably in many respects from that of other cells, data obtained on amphibia or birds are only of limited value for the understanding and perhaps prediction of processes during the normal or pathological development within mammalian species. Some years ago we, therefore, started a survey on several main metabolic pathways in mammalian embryonic tissues in order to gain a better understanding of the metabolism as it proceeds in these tissues during development and to learn more about the mode of action of embryotoxic agents. In this paper some of the aspects of our recent studies are presented and some of the difficulties limiting our understanding of possible interference with mammalian developmental processes are revealed. Three points will be discussed: the choice of methods used in such studies, some examples of special biochemical peculiarities of mammalian embryonic tissue and the action of some embryotoxic agents on biochemical reactions in mammalian embryonic tissue. We feel it necessary to stress that pertinent information can be obtained only when a combination of different biochemical and morphological methods is used. Such methods include studies on the enzyme kinetics in multi-enzyme systems and on whole embryos in vitro and in vivo as well as a combination of light microscopical, electron microscopical, radioautographical and tissue culture studies. Therefore, such studies can be performed only as a joint project by biochemical, pharmacological and morphological groups. From the biochemical reactions that might differ quantitatively or even qualitatively from corresponding reactions occuring in cells of an adult organism some aspects of nucleic acid metabolism and some features of energy and glucose metabolism are discussed. The studies on nucleic acid metabolism include experiments with cell fractions isolated from embryonic tissue and incorporation studies with radioactively labelled precursors. The studies on energy metabolism include experiments on aerobic glycolysis in mammalian embryonic tissue as well as studies on pentose phosphate pathway. In a third part some examples of substances – known to produce embryotoxic effects – are selected and several sets of experiments on metabolic reactions as modified by these agents are presented. The embryotoxic substances used include the antimetabolite 6–aminonicotinamidc (6–AN), the alkylating agent cyclophosphamide (Endoxan) and thalidomide. As far as possible.the biochemical studies have been combined with morphological, especially electron microscopical, observations.