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Evidence of DNA binding activity of perchloroethylene
M Mazzullo1, S Grilli, G Lattanzi
1Centro Interuniversitario per la Ricerca sul Cancro, Università di Bologna, Italy.
Abstract:
14C-Perchloroethylene is covalently bound to DNA, RNA and proteins of rat and mouse organs in vivo after ip injection. Covalent Binding Index values are typical of weak-moderate and weak initiators, for mouse and rat liver, respectively. The greater amounts of labelings detected in mouse liver and in rat kidney macromolecules are consistent with the known toxic and carcinogenic actions of this compound. In vitro binding of perchloroethylene to nucleic acids and proteins proceeds through the involvement of the P-450-dependent mixed function oxidase system from liver microsomes. Kidney, lung and stomach microsomal fractions are uneffective. Cytosolic enzymes from all assayed organs are much more efficient than liver microsomes in bioactivating the compound. GSH addition to liver microsomal system greatly enhances binding extent. This observation suggests that GSH plays a role in the binding of perchloroethylene metabolites as for symmetrically substituted haloethanes.