Cross-linking of glutathione to DNA by cancer chemotherapeutic platinum coordination complexes.

Glutathione can modulate the toxicity of a variety of drugs, although its role in modulating toxicity by anticancer platinum drugs is ambivalent. At physiologically relevant concentrations, glutathione can inhibit the reaction between DNA and cis-dichloro(ethylenediamine)platinum(II) (cis-DEP). Glutathione can also react with monofunctional adducts in DNA to produce a glutathione-Pt-deoxyguanosine cross-link which would reduce the potential toxicity of the drug. The relative importance of these two mechanisms of detoxification is unknown, although both mechanisms probably contribute to glutathione modulation of platinum toxicity.