Mechanism and Response in Cellular Toxicity

There are many different mechanisms underlying toxicity, leading to the different types of responses. However, most toxicity is due to the interaction between the ultimate toxicant and a target molecule. The ultimate toxicant may be a reactive metabolite, a stable metabolite, or the parent compound. The molecule could be part of a structure, the cell membrane, for example, or an individual macromolecule such as an enzyme. 

There are different types of reaction that could occur  

Clearly, nucleophilic toxicants will react with electrophilic sites in target molecules but is not common. Carbon monoxide and cyanide are good examples where the electrophilic site in both cases is the heme group in proteins. Hydrazines will react with the electrophilic carbonyl carbon in keto groups such as in pyridoxal phosphate. 

It may have different outcomes ranging from genetic damage to immune responses. This is true of all interactions between chemicals and macromolecules, as will be seen later in this chapter and in chapter 7. 

Non-covalent bonding includes hydrogen bonding, ionic bonds, or hydrophobic bonds. These types of bonding are involved in binding of chemicals to plasma proteins. They could also underlie the interaction between a chemical and a receptor or enzyme. Thus, the interaction between TCDD and the Ah receptor (AhR) and the intercalation of doxorubicin in DNA involve non-covalent bonds. 

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