HIGH-VALENT Cr, Mn, AND Fe SPECIES - Oxidation of Amino Acids, Peptides, and Proteins: Kinetics and Mechanism - page 302

dysregulated survival signaling and transcriptional repatterning are involved
in the mechanisms of death resistance. Studies have demonstrated in the
Cr(VI) exposure to the cells that the phosphorylation of proteins, which
regulates the dysregulation processes, provides a critical molecular switch for
rapid control of signaling pathways [173]. Signaling pathways include serine/
threonine protein kinases that sense DNA damage and activate p53 and pro-
liferating protein tyrosine kinase cascades, and cell death/cell growth-arresting
tyrosine phosphatases. Tissue injury and severe inflammatory responses may
result from direct exposure of Cr(VI) to the cells (Fig. 6.12). Therefore, there
may be a further contribution to the microenvironment potentiating the death
resistance phenotype to participate in early-stage carcinogenesis. This phe-
nomenon over time may lead to the malignant conversion of the predisposed
precursor cells to tumor cells [129]. In a recent study, it was demonstrated that
Cr(VI) could induce genes [128]. It was postulated that the exposure of Cr(VI)
stimulates gene Fyn to initiate innate immune gene induction in human airway
epithelial cells through an innate immune-like signal transducer and activator
of transcription 1 (STAT1)-dependent pathway [128].

6.1.8 Conclusions

Compounds of high-valent species of Cr have roles in developing new materi-
als and in causing carcinogenic and toxic effects. Formations of Cr(V) an
Cr(IV) in the reduction of Cr(VI) by substrates of biological importance have
been suggested and, in some cases, direct spectroscopic evidences were given
to suggest the formation of Cr(V) and Cr(IV) complexes. Reactive oxygen
species O •− and • OH have also been proposed in the metabolism of Cr(VI).
A multistage-multipath mechanism may be involved in causing cancer by
Cr(VI). The oxidation of thioredoxin and peroxiredoxins by Cr(VI) is feasible
and has implication in biological systems. Progress has been made to under-
stand the genotoxicity and mutagenicity of Cr(VI) in vitro and in vivo ; however,
additional studies are needed to comprehend the mechanism of chromium
carcinogenicity. The identification of high-valent Cr species, formed in vivo ,
in future studies may include the application of EPR and rapid synchrotron
X-ray fluorescence mapping with XANES. Lastly, the Cr(VI)/H 2 O 2 system
may be applied to the oxidation of organic pollutants in water.

6.2 MANGANESE

Manganese compounds with oxidation states varying from −1 to +7 have been
synthesized. Examples of Mn(−1) and Mn(O) compounds are the Mn C( ) −
ion and Mn 2 (CO) 10 , respectively [174]. The Mn + ion does not exist in aqueous
solution, but the +1 oxidation state is present in the [Mn(CN) 6 ] 5− ion. Mn 2+
is stable over a wide range of potentials in acidic solutions. However, Mn 2+