Environ Health Perspect. 1978 Jun;24:87-100. doi: 10.1289/ehp.782487.
Cytotoxic chemicals have in common the ability to act specifically on cells in cycle. Bacteria are more sensitive in the exponential growth phase than when growing slowly in media. Similar observations have been made on a variety of systems ranging from bacteria, yeast, higher plants and invertebrates to vertebrates including primates. The embryo and fetus are highly susceptible to cytotoxic agents because they have continuous groups of cells in the growth phase. Acutely toxic doses may cause cellular death and result in developmental defects or fetal death. Cytotoxic agents can be grouped as alkylating agents, electrophilic reactants, antimetabolites, intercalating agents, amino acid antagonists, spindle poisons, and an additional group of chemicals which covalently bind to DNA. These cytotoxic groups of chemicals may also be mutagenic by interacting with DNA to produce changes in sequences of nucleotides resulting in heritable defects either in a somatic cell line or in a germinal cell line. The mechanisms of chemical-induced teratogenicity and mutagenicity are similar. This commonality is further discussed in the text.
细胞毒性化学物质具有特异性作用于细胞周期的能力。细菌在指数生长阶段比在缓慢生长的培养基中更为敏感。从细菌、酵母、高等植物和无脊椎动物到包括灵长类动物在内的脊椎动物等各种系统中都观察到了类似的现象。胚胎和胎儿对细胞毒性剂非常敏感,因为它们在生长阶段有连续的细胞群。急性毒性剂量可能导致细胞死亡,并导致发育缺陷或胎儿死亡。细胞毒性剂可以分为烷化剂、亲电试剂、抗代谢物、嵌入剂、氨基酸拮抗剂、纺锤体毒物,以及另一组与 DNA 共价结合的化学物质。这些细胞毒性化学物质也可能通过与 DNA 相互作用导致核苷酸序列发生变化,从而在体细胞系或生殖细胞系中产生可遗传的缺陷,从而具有致突变性。化学物质引起致畸性和致突变性的机制相似。在正文中进一步讨论了这种共性。