Interaction with Toxic Transition Metals

Biological effects of some transition metal ions on DNA were associated with their mutagenic and carcinogen actions (Sissoeff et al. 1976, Kazantsis et al. 1979). Various studies in eredopathology and toxicology have shown that some M induce malformations and teratogenic effects. 

Experimental investigations were mainly convened with metals of group VIII, namely Fe , Co, and Ni . These metals form covalent bonds with the N atoms of DNA, producing pronounced destabilization of the double helix with harmful biological consequences. 

There are cases when heavy metals are used in chemotherapy, for example cytostatic chemotherapy with as-platinum (Rosenberg 1969 [cited by Lippert 1999], Garban etal. 1989, Haiduc and Silvestru 1989, Johnsson et al. 1995). Numerous research studies into the interaction of DNA with metal ions also dealt with ds-platinum (Lippert 1999, Garban 2000). Cis-platinum interacts with nucleosides preferentially through the Ny site of guanine, but may also form bidentate chelates as a result of interaction both with Ny and sites. Modifications induced to ds-platinum by the interaction with guanine have been studied using quantum chemistry (Lippert 1999, Chojnacki et al. 2001). 

Some metal compounds have been studied in vitro for their antitumoral effects and antiarthritic effects (Gielen et al. 1994, Sadler and Sue 1994), following the interac- 

Many carcinogens, which implicitly are metals with toxicogenic potential, bind directly to the DNA chain, forming an adduct and lowering the ionization potential of the DNA. 

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Injury to cells and tissues may enhance the toxicity of the active oxygen species by releasing intracellular transition metal ions (such as iron) into the surrounding tissue from storage sites, decompartmentalized haem proteins, or metalloproteins by interaction with delocalized proteases or oxidants. Such delocalized iron and haem proteins have the capacity to decompose peroxide to peroxyl and alkoxyl radicals, exacerbating the initial lesion. 

A review article has appeared (237) which discusses the biological activity of thioethers and their derivatives with particular reference to interactions with transition-metal ions. Accordingly, only some of the more salient points will be discussed here. In any biological studies, the toxicity of Me2SO 482) and of its transition-metal complexes 140) should be borne in mind. 

Metal ions play an important role in the stabilization of DNA and in the catalytic activity of DNA polymerases [1], Transition metals like Mn and Co, etc., at higher ionic strength are found to be mutagenic and carcinogenic in nature and also change the helical nature of the DNA [1-6]. Aluminum (Al) is reported to be associated with neurological disorders and to cause cellular toxicity through its interaction with DNA in cells [7-9]. 

ROS may also affect microorganisms through the production of toxic trace metal species. For example, the photolysis of organic Cu-complexes and interactions with 02 may increase the Cu bioavailability and hence Cu toxicity to phytoplankton. This interaction with transition metals is likely to be one of the main processes through which photochemically produced 02 , or other charged ROS, can have an adverse affect on aquatic biota but further studies are needed to ascertain the ecological impact of these types of reactions in natural waters. 

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