Relationship Between Structure and Mutagenic/Carcinogenic Activity of Short Chain Aliphatic Halocompounds: A Collaborative Project
The halogenated hydrocarbons represent one of the most important categories of industrial chemicals owing to their use, production volume, environmental and toxicological activity and, hence most important, potential population risk. They are probably the most ubiquitous in occurrence. A number of these, because of their use as pesticides and aerosol propellents and their high chemical stabilities, have become distributed throughout the biosphere. Occupational exposure, seems to be the major risk1. In fact, several of these compounds are carcinogens in test animals2,3,4 and their acute and chronic toxic effects on liver, kidney and central nervous system have been demonstrated5,6. However, in most cases, no adequate human data are available for estimating risk by halocompounds. They react with nucleophilic substrates by direct attack or after bioactivation by enzymatic systems. The direct reactivity of halocompounds decreases from iodo- to bromo- and chloro-substituted compounds. More generally, halocompounds are enzymatically “activated” to interact with macromolecules. The first metabolic step is an oxidation due to the mixed function oxidase system (MFO) in the presence of cytochrome P-450 with the exception of carbon tetrachloride and halothane metabolism where initial reductive reactions by MFO occur. Oxidation by P-450 dependent-MFO activity results in the addition of radical oxene to the carbon-carbon bond of substrate that leads to epoxide formation.
KeywordsQuantitative Structure Activity Relationship Fragile Site Logarithmic Growth Phase Mixed Function Oxidase Mixed Function Oxidase System
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