Susan W. C. Leuthauser

The effect of iron on the distribution of superoxide and hydroxyl radicals as seen by spin trapping and on the superoxide dismutase assay.

Abstract— Using the spin trap 5,5‐dimethyl‐1‐pyrroline‐1‐oxide we have demonstrated the presence of OH in the xanthine‐xanthine oxidase system when iron and/or iron‐EDTA (ethylenediamine‐tetraacetic acid) is present. With increasing iron (or iron‐EDTA) concentration the intensity of the O2‐ spin adduct decreased while that of OH increased. However, use of diethylenetriaminepentaacetic acid (DETAPAC) as a metal chelator in the reaction mixture suppressed the OH spin adduct signal while maintaining the intensity of the signal from the O2‐ spin adduct.

Copper complexes: a physiological approach to the treatment of ‘inflammatory diseases’

Abstract Plasma concentrations of low molecular weight copper-containing components are known to increase in response to arthritis, epilepsy, and cancer. Each of these diseases are recognized as having inflammatory components. Evidence is provided to show that administration of low molecular weight copper complexes produce antiinflammatory effects in animal models of inflammation, anticonvulsant effects in animal models of seizure, and anticancer effects in animal models of cancer. These data are reviewed in support of the hypothesis that the elevation of plasma copper-containing components represents a physiologic response which may lead to remission. Promotion of this physiologic response would appear to be a valid approach to the treatment of arthritis, epilepsy, cancer, and other diseases with inflammatory components.

Anticancer activity of metal compounds with superoxide dismutase activity

LARRY W. OBERLEY I, S.W.C. LEUTHAUSER l, ROBERT F. PASTERNACK 2, TERRY D. OBERLEY 3, LOREN SCHUTT J and JOHN R. J. SORENSON 4 JRadiation Research Laboratory, 14 Medical Laboratories, The University of Iowa, Iowa City, Iowa 52242, USA 2Department of Chemistry, Ithaca College, Ithaca, New York 14850, USA, 3Department of Pathology and Immunobiology Research Center, University of Wisconsin, 470 North Charter Street, Madison, Wisconsin 53706, USA, and 4College of Pharmacy, University of Arkansas Medical Sciences Campus, 4301 West Markham Street, Little Rock, Arkansas 72201, USA

Pharmacologic Activities of Copper Compounds in Chronic Diseases

Copper complexes have been shown to be effective antiinflammatory, antiulcer, anticonvulsant, anticancer, and antidiabetic agents. This seemingly diverse variety of pharmacologic effects is unified by the hypothesis that copper complexes facilitate or promote tissue repair processes involving copper-dependent enzymes and that arthritis, ulcers, seizures, neoplasia, and diabetes are diseases of specific tissues in disrepair. The corollary to this hypothesis is that the loss or reduction of copper-dependent enzyme-mediated processes leads to tissue dysfunction that may be reversed with copper complex therapy.

Induction of cytodifferentiation in C3H/10T 12 mouse embryo cells by X-irradiation and benzo(a)pyrene

5-Azacytidine has been reported to induce adipogenesis and myogenesis in C3H/10T1/2 mouse cells. Additionally, this agent will produce neoplastic transformation of C3H/10T1/2 cells. Very little other data is available regarding induction of differentiation by oncogenic agents. We report here that benzo(a)pyrene and X-irradiation induce a consistent frequency of adipogenesis in C3H/10T1/2 cells. The frequency of induced differentiation is similar to the frequency of the transformation event caused by these agents.

Thyroid hormone affects the expression of neoplastic transformation induced by DNA-transfection

Thyroid hormone can dramatically modulate oncogenic transformation of cells in culture. To further investigate this we have used DNA-mediated gene transfer (transfection) to transform cells grown in the presence (+T3) or absence (-T3) of thyroid hormones. Removal of thyroid hormones from the culture media greatly reduced the appearance of transformed foci subsequent to transfection. However, +T3 or -T3 media had no effect on the appearance of ouabain-resistant (ouar) colonies following transfection of ouabain-sensitive (ouas) cells with DNA isolated from ouar cells and selection in 3 mM ouabain. These results suggest that thyroid hormone does not effect the uptake or integration of exogenous DNA, but instead may modify the expression of transformation.

Antitumor SOD Compounds

Many studies have been recently performed on the activity of the enzyme superoxide dismutase (SOD) in tumor cells. This enzyme catalyzes the reaction \(\\{20_2}^{\bar .}\; + \;2H\; \to {H_2}{0_2}\; + \;{0_2}\;(1)\). SOD is thought to be a protective enzyme necessary for life in all oxygen metabolizing cells (2). All normal eukaryotic cells (except the red blood cell) have both copper-zinc containing superoxide dismutase activity (Cu-ZnSOD) and manganese containing superoxide dismutase activity (MnSOD) (3). A typical pattern has emerged from the studies of SOD in tumor cells. Cancer cells have in general lowered activities of both Cu-ZnSOD and MnSOD when compared to their differentiated normal cell counterparts. Exceptions have been found to this pattern of low Cu-ZnSOD activity, but no exceptions have been found in the case of MnSOD activity. MnSOD activity has been found to be greatly reduced in over 50 human, rat, mouse, spontaneous, transplanted, virallyinduced, chemically-induced, in vivo, and in vitro tumors. This work has been the subject of a recent review (4).