Our Science – Kasprzak Website
Kazimierz S. Kasprzak, Ph.D.
Dr. Kasprzak's research has been devoted to understanding the chemical and biological mechanisms involved in the induction of occupational cancer in humans exposed to heavy metals, nickel in particular. The mechanisms encompass a wide variety of interactions between a given metal ion and target bio-molecules resulting in structural and functional alterations of such molecules. His original discoveries in this field include demonstration of renal cancer initiation by soluble nickel compounds and identification of pro-mutagenic DNA base products, typical for oxidative damage in animal kidneys exposed to nickel or cobalt that might be responsible for tumor initiation through genotoxic mechanisms. In the follow-up studies, Dr. Kasprzak's group found that the observed oxidative DNA damage could be facilitated by nickel(II) ions bound to unique amino acid sequences in core histones H3 and H2A. Most notably, nickel binding to H2A also resulted in a site-specific hydrolytic cleavage of this histone's C-terminal tail. The cleavage modifies chromatin structure and affects gene expression that may contribute to carcinogenesis through epigenetic mechanisms. Studies on oxidative damage induced by some transition metals in in vitro and in vivo systems brought Dr. Kasprzak's team to yet another critical target molecule, ascorbic acid. The latter, a major cellular antioxidant, is depleted through metal-catalyzed oxidation. This has many pathogenic consequences to the cell, e.g., activation of genes normally responding to hypoxia, inhibition of repair of alkylated DNA bases, and disturbances in collagen formation. All this occurs because of inhibition of non-heme hydroxylases that utilize ascorbate as a co-factor. A key discovery resulting from this avenue of his research was that the above pathogenic effects of metals can be alleviated by ascorbic acid supplementation.
Currently, Dr. Kasprzak continues to consult NTP, review papers for scientific journals and write reviews and book chapters on metal toxicology and carcinogenesis.
This page was last updated on 2/27/2013.