HIGH-VALENT Cr, Mn, AND Fe SPECIES - Oxidation of Amino Acids, Peptides, and Proteins: Kinetics and Mechanism - page 297

300

Protein carbonyl
DNA-protein cross-link coefficient

200

100

0

Figure 6.9. Effect of antioxidants and cellular chromate reductants on potassium
chromate-induced protein oxidation and DNA-protein cross-linking. Cells were
retreated with the respective agents in a complete medium for 16 hours, washed, and
then treated with 200 µM chromate for 2 hours in salts-glucose medium (adapted from
Mattagajasingh et al. [155] with the permission of Wiley Inc.).

results of Figure 6.9. This is supported by increased levels of Cr(VI)-induced
DPCs and protein carbonyls in riboflavin pretreated cells. Furthermore, it is
also supported by the use of a known catalase inhibitor, aminotriazole, in the
pretreatment of cells in which an increase in Cr(VI)-induced DPCs and protein
carbonyls by 67% and 66%, respectively, were observed (Fig. 6.9). A separate
study has also shown that Cr(V) species produced from Cr(VI) can also
oxidize human orosomucoid (α 1 -acid glycoprotein) [156].
A primary cause of genetic lesions induced by Cr(VI) in mammalian cells
was suggested due to the formation of the chromium-DNA adduct [124, 140,
157, 158]. Other types of adducts in the Cr-DNA are between Cr(III)-ligand-
DNA complexes, which can be either binary or ternary. Among several adducts,
ternary adducts are more relevant due to their abundance and importance in
toxicology [124, 140, 157, 158]. Cr(III)-histidine-, Cr(III)-ascorbate-, Cr(III)-
cysteine-, and Cr(III)-GSH-DNA adducts are examples of ternary adducts
that are present after exposure and intracellular reduction of Cr(VI). DNA-
chromium-DNA cross-links and DNA-chromium-GSH cross-links were sug-
gested to cause significant damage to DNA [159] The role of Cr(V) in the
oxidation of DNA has been examined by studying the reactions of Cr(V)