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Hard electrophiles including DNA-reactive metabolites (e.g., electrophilic carbonyl compounds) will preferentially react with hard nucleophiles such as amines (e.g., semicarbazide and methoxylamine), amino acids (e.g., lysine), and DNA bases (e.g., guanine and cytosine) affording the corresponding Schiff bases.40 Likewise, the cyanide anion, N-acetyllysine and methoxylamine are ‘hard’ nucleophiles that can be used to trap hard electrophiles such as electrophilic iminium species that are generated via metabolism of tertiary amines.99,100 Usually GSH conjugate screening is performed on samples generated in vitro (using microsomes or hepatocytes), because in vivo, the conjugates might be transported to bile and destroyed by gut bacteria
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