Kozuka H
Department of Toxicology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Yakugaku Zasshi. 1995 Mar;115(3):157-69. doi: 10.1248/yakushi1947.115.3_157.
"Toxicology" includes a broad range of application such as environmental, clinical and forensic toxicology. These several kinds of applied toxicology forms a mutually connected ring. This ring is supported by a column called as deductive and detective analysis by the author. "Deductive toxicology" is a way of thinking to solve toxicological problems more multidimensionally. In this paper, an application of this way to the study of bone lesions observed in Itai-itai diseased patients is described. In cultured embryonic chick bone, both cadmium and copper induced an atrophic change of the osseous tissue. However, zinc induced an osteomalacic change as a result of strong inhibition of calcification. These histological changes were supported by investigation using a culture system of osteoblastic MC3T3-E1 cells. Cadmium stimulated bone resorption in a neonatal parietal bone. In addition, cadmium stimulated the formation of osteoclast-like cells in bone marrow cell culture. It is thus suggested that cadmium and copper are factors of osteoporosis whereas zinc is a factor of osteomalacia when they directly act on bone tissues. A simultaneous exposure of cadmium and zinc to cultured bones resulted in an osteomalacic change with or without inhibition of bone matrix formation. Copper caused an atrophic change in the absence or the presence of zinc. A combination of cadmium and copper induced a severe damage of osteoblasts and osteogenic mesenchymal cells. These results suggested that an interactive exhibition of heavy metal toxicity can cause various bone lesions such as osteomalacia, osteoporosis and osteoporomalacia. The idea that heavy metals can directly act on bone tissues and their interaction can induce various histological changes in the tissue will help an understanding of bone lesions in Itai-itai disease.
“毒理学”涵盖了广泛的应用领域，如环境毒理学、临床毒理学和法医毒理学等。这几种应用毒理学形成了一个相互关联的环。作者将这个环建立在一个名为演绎与侦探分析的支柱之上。“演绎毒理学”是一种从更多维度解决毒理学问题的思维方式。本文描述了这种方法在痛痛病患者骨病变研究中的应用。在培养的鸡胚骨中，镉和铜均诱导了骨组织的萎缩性变化。然而，锌由于对钙化的强烈抑制作用而导致骨软化性变化。这些组织学变化得到了使用成骨细胞MC3T3 - E1细胞培养系统进行研究的支持。镉刺激新生顶骨的骨吸收。此外，镉在骨髓细胞培养中刺激破骨细胞样细胞的形成。因此表明，镉和铜是骨质疏松的因素，而锌直接作用于骨组织时是骨软化的因素。镉和锌同时作用于培养的骨会导致骨软化性变化，且可能伴有或不伴有骨基质形成的抑制。无论有无锌存在，铜都会引起萎缩性变化。镉和铜的组合会导致成骨细胞和骨源性间充质细胞的严重损伤。这些结果表明，重金属毒性的相互作用表现可导致各种骨病变，如骨软化、骨质疏松和骨质疏松性骨软化。重金属可直接作用于骨组织且它们的相互作用可诱导组织发生各种组织学变化的观点，将有助于理解痛痛病中的骨病变。
