Inhibition mechanism, 224 Xenobiotics, function

The biochemical aspects of teratology are not particularly well understood. Several kinds of biochemical mechanisms are probably involved. One such mechanism is interference with DNA synthesis, which alters the function of nucleic acids in cell replications, resulting in effects that are expressed as birth defects. Exposure to teratogenic xenobiotic substances may result in either an absence or excess of chromosomes. Enzyme inhibition (see Section 7.6) by xenobiotics can result in birth defects. Xenobiotics that deprive the fetus of essential substrates (for example, vitamins), that interfere with energy supply, or that alter the permeability of the placental membrane may all cause birth defects. 

The traditional scientific approach to pharmaceutical safety assessment was based largely on the concept of xenobiotic-mediated direct injury to the whole animal, organ, tissue, or cell manifested by death altered function or modified growth rates. As scientific knowledge advanced, it became apparent that a variety of mechanisms were involved including direct injury to cellular macromolecules (e.g., DNA, RNA, proteins) or organelles (e.g., mitochondria, endoplasmic reticulum), adaptive responses (e.g., induction or inhibition of cyto-... 

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