Adduct 323 Biomolecules

High-performance liquid chromatography-mass spectrometry (HPLC-MS) is a powerful analytical technique widely used in recent years for the analysis of biomarkers and metabolites. Biomarker determination and quantification, whether metabolic or adducted biomolecules, are commonly used to evaluate exposure and support biomonitoring research, especially in the area of occupational exposure and health. Some of the common problems and strategies of HPLC-MS biomarker analysis involve matrix effects, the use of isotope-labeled internal standard compounds, and sample cleanup usually all of these factors must be evaluated within the development phase of an analysis procedure. Specific examples of biomarker analysis using HPLC-MS include acrylamide, aromatic compounds, and 1-bromopropane, and these examples are discussed in detail. 

The reaction of sulfur-containing biomolecules with platinum antitumor compounds, thereby preventing binding to the critical DNA target, is a possible mechanism of inactivation and is supported by numerous studies. Thus, glutathione (GSH, a cysteine-containing tripeptide see also Fig. 6), which is the predominant intracellular thiol and is present in concentrations varying from 0.5 to 10 mM, is able to inhibit the reaction of DNA with [Pt(en)Cl2] (74) and with cis-Pt (75, 76). It has also been observed that the presence of cysteine can inhibit the reaction between cis-Pt and d-Guo (77). Furthermore, the antitumor activity of cis-Pt was proved to be inhibited by coadministered methionine (78, 79) and even a bis-adduct between cis-Pt and methionine has been isolated from the urine of patients (80). 

A second mechanism of inactivation might be the reaction of sulfur-containing biomolecules with the cis-Pt-DNA monoadducts (product 1 in Fig. 4), which prevents those from rearranging to toxic bifunctional adducts. Supportive for such a mechanism is the observation that GSH can be cross-linked to DNA by cis-Pt (41,41a) and [Pt(en)Cl2] (74), and that cysteine can be cross-linked to d-Guo by cis-Pt (77). Furthermore, cis-Pt-DNA monoadducts can be experimentally quenched with thiourea, which reduces drug toxicity (82, 83). trans-Pt also yields monofunctional adducts after reaction with DNA, and these rearrange somewhat slower than does cis-Pt into bifunctional adducts (41,84), clearly for sterical reasons. The relatively long-living monofunctional adducts react efficiently with GSH and proteins (41 a, 84-86). 

A particularly useful kind of biomarker used with increasing frequency during recent years consists of adducts of xenobiotics or their metabolites to biomolecules. A particularly straightforward example of such an adduct measured for many years as evidence of exposure is carboxyhe-moglobin, COHb, produced when inhaled carbon monoxide adds to blood hemoglobin, Hb ... 

Which biomolecule is most commonly involved in the formation of adducts for biological monitoring What is a problem with measuring adducts for biological monitoring ... 

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