Lansdown Alan B G
Chemical Pathology, Faculty of Medicine, Imperial College London, Charing Cross Campus, London W6 8RP, UK.
Met Ions Life Sci. 2011;8:187-246. doi: 10.1039/9781849732116-00187.
The skin and eyes remain in constant exposure to the surrounding environment and are subject to accidental, occupational, and biological risks at all times, Normal development, homeostasis, and repair following injury depend upon appropriate levels of calcium, zinc, magnesium, copper, iron, and minute amounts of other trace metals. Both tissues exist in a permanent state of dynamic equilibrium with the environment whereby cells lost through natural wear and tear are replaced through genetically regulated mitotic patterns. Normal functional requirements of the constituent tissues depend on critical balances between trace metals, metal ion gradients, and specific carrier proteins which are modulated by upregulation of growth factors, cytokines, hormones, and subcellular regulators acting by autocrine, paracrine, and endocrine mechanisms. Metal ion gradients in epidermal tissues serve critical functions in basal cell proliferation, post-mitotic migration, and functional differentiation in normal homeostasis and in repair following injury. Toxic mechanisms reflect imbalances in trace metals or interaction between xenobiotic and trace metals through competitive binding key carrier proteins and metabolic pathways leading to trace metal imbalances and functional impairment. Alternatively, toxic injuries result through direct cytotoxic action of metal ions on cell membranes, intercellular communication, RNA and DNA damage, and mutagenic change. Arsenic is the only primary carcinogen in the skin following ingestion or topical exposure; beryllium, aluminum, and zirconium are a cause of granuloma. Aluminum as a cause for breast cancer is equivocal. Metal toxicities in the eye result from direct accidental or occupational exposure and systemic uptake of neurotoxic metals and their action on the retina and optic nerve. Calcium, zinc, magnesium, and iron are essential trace elements in eye development and physiology but silver, gold, lead, and mercury are absorbed through optic membranes or from the circulation to accumulate in the vitreous leading to local or systemic action. Lead, mercury, cadmium, aluminum, and other xenobiotic metals are implicated in structural and physiological damage in the mammalian eye. Thallium shows an affinity for melanin.
皮肤和眼睛始终处于与周围环境的持续接触中，时刻面临意外、职业和生物风险。正常发育、体内平衡以及损伤后的修复取决于钙、锌、镁、铜、铁以及其他微量金属的适当水平。这两种组织都与环境处于永久的动态平衡状态，通过基因调控的有丝分裂模式替代因自然磨损而损失的细胞。组成组织的正常功能需求取决于微量金属、金属离子梯度和特定载体蛋白之间的关键平衡，这些平衡由通过自分泌、旁分泌和内分泌机制起作用的生长因子、细胞因子、激素和亚细胞调节因子的上调来调节。表皮组织中的金属离子梯度在正常体内平衡和损伤修复过程中对基底细胞增殖、有丝分裂后迁移和功能分化起着关键作用。毒性机制反映了微量金属的失衡，或外源性物质与微量金属通过竞争性结合关键载体蛋白和代谢途径相互作用，导致微量金属失衡和功能损害。或者，毒性损伤是通过金属离子对细胞膜的直接细胞毒性作用、细胞间通讯、RNA和DNA损伤以及诱变改变而产生的。砷是摄入或局部接触后皮肤中唯一的主要致癌物；铍、铝和锆是肉芽肿的病因。铝作为乳腺癌的病因尚不明确。眼睛中的金属毒性源于直接的意外或职业接触以及神经毒性金属的全身吸收及其对视网膜和视神经的作用。钙、锌、镁和铁是眼睛发育和生理过程中的必需微量元素，但银、金、铅和汞通过视神经膜或从循环中吸收，在玻璃体中积累，导致局部或全身作用。铅、汞、镉、铝和其他外源性金属与哺乳动物眼睛的结构和生理损伤有关。铊对黑色素有亲和力。
