Properties of the reaction of cis-dichlorodiammineplatinum(II) with metallothionein.

Properties of the reactions of cis-dichlorodiammine Pt(II) and related complexes with zinc metallothionein or apometallothionein have been investigated. During these reactions, platinum binds stoichiometrically to protein sulfhydryl groups and zinc, if present, is displaced. The ammine ligands are also lost in the process, suggesting that Pt(II) has tetrathiolate coordination in metallothionein.

Surreptitious lead exposure from an Asian Indian medication.

A case of lead exposure resulting from the ingestion of a lead-containing medication is reported. The ingestion was detected during routine biological monitoring for lead exposure conducted on all workers of a lead-acid battery plant where the subject was employed. A case history, including the results of periodic blood lead, hemoglobin, and protoporphyrin analysis, and analysis of the medication, is provided.

Chromium determinations in a case of chromic acid ingestion.

A fatal case of acute chromic acid ingestion is reported. The case history and biological fluid concentrations of chromium are presented and discussed. Previous cases of acute chromium intoxication are reviewed and recommendations for the management of such patients are presented.

Arsenic content of homeopathic medicines.

In order to test the widely held assumption that homeopathic medicines contain negligible quantities of their major ingredients, six such medicines labeled in Latin as containing arsenic were purchased over the counter and by mail order and their arsenic contents measured. Values determined were similar to those expected from label information in only two of six and were markedly at variance in the remaining four. Arsenic was present in notable quantities in two preparations.

Gold induced aplastic anemia. Complete response to corticosteroids, plasmapheresis, and N-acetylcysteine infusion.

A 47-year-old woman with rheumatoid arthritis (RA) had been treated with greater than 7 g of gold sodium thiomalate over a 5 year period when aplastic anemia developed. Treatment with corticosteroids, plasmapheresis and infusion of N-acetylcysteine (NAC) resulted in complete hematologic remission. Infusion of NAC increased daily urinary excretion of gold and use of an ambulatory infusion pump with a Hickman catheter allowed protracted outpatient infusion for more than 4 months' duration.

Studies on the chemical reactivity of copper bleomycin.

The copper(II) complex of the clinically used antitumor agent bleomycin (Blm) has cytotoxic as well as antitumor properties. To understand the relationship of the bleomycin ligand, copper bleomycin, and other possible metal complexes of this agent, kinetic studies of the formation of Cu(II)Blm, ligand substitution reactions of CuBlm with ethylenediaminetetraaletic acid, and the redox reaction of CuBlm with thiols have been completed and interpreted along with previous studies of the thermodynamic stability of Cu2+ with bleomycin. Cu(II)Bm is found to be kinetically and thermodynamically stable in ligand substitution processes and is only slowly reduced and dissociated by sulfhydryl reagents.

Interactions among iron(II) bleomycin, Lewis bases, and DNA.

The interaction of sulfur-containing ligands with complexes of Fe(II) bleomycin [Fe(II)Blm] was investigated by comparing DNA strand-scission activity with the structural characteristics of the complex. The bithiazole ring of excess Blm can form intermolecular complexes with Fe(II)Blm and with NO-Fe(II)Blm, and the bithiazole groups of CO-Fe(II)Blm interact with the metal center. This binding can be reversed by glutathione, CO-Fe(II)Blm binds to poly(dA-dT) .

Cytotoxic and antitumor properties of bleomycin and several of its metal complexes.

This study examines the concentration-dependent cytotoxicity and antitumor activity of bleomycin (Blm) and Cu-, Zn-, Fe(III)-, and CoBlm using Ehrlich cells in culture and the Ehrlich ascites tumor. The order of activity in culture under several conditions is CuBlm approximately equal to Blm approximately equal to ZnBlm > Fe(III)Blm > CoBlm approximately equal to control. Short exposures of cells to drugs in the presence or absence of serum produced effects on cell proliferation similar to 48-h incubations.

Effects of ethylenediaminetetraacetic acid and 1,10-phenanthroline on cell proliferation and DNA synthesis of Ehrlich ascites cells.

The interactions of ethylenediaminetetraacetic acid (EDTA) and 1,10-phenanthroline with Ehrlich cells have been studied. Both compounds inhibit proliferation of cells in culture. After long-term incubation of cells with these metal-chelating agents under conditions in which cell viability is not impaired but proliferation is retarded, the rate of DNA synthesis of EDTA-exposed cells is the same as that of untreated controls, whereas the rate of DNA synthesis of 1,10-phenanthroline-exposed cells is markedly reduced.

Zinc-, copper- and cadmium-binding protein in Ehrlich ascites tumour cells.

The properties of Ehrlich ascites tumour cells exposed in vivo to cadmium were investigated as a function of the zinc status of the host animals. Tumour-cell growth was inhibited by cadmium in both zinc-sufficient and zinc-deficient animals. However, cells in zinc-sufficient tumours accumulate much less cadmium than those in deficient tumours.

Comparative cytotoxic and biochemical effects of ligands and metal complexes of alpha-N-heterocyclic carboxaldehyde thiosemicarbazones.

Several alpha-N-heterocyclic carboxaldehyde thiosemicarbazones and their iron and copper complexes have been tested for their cytotoxicity and inhibiting activity against DNA synthesis under controlled metal conditions. No ligands show cytotoxicity against Ehrlich cells at the concentrations tested, while some iron and copper complexes are active. In contrast, the ligands inhibit DNA synthesis at much lower concentrations than used above.

Zinc deficiency and growth of Ehrlich ascites tumor.

The growth rate of Ehrlich ascites tumors has been examined as a function of the zinc content of the diet of the host mice. Imposition of a diet containing a low amount of zinc (1 microgram/g) on the day of tumor transplant leads to a marked retardation in growth. Pretreatment of the mice with this diet slows the growth further so that the lifetime of the mice can be doubled.

Control of Ehrlich cell division by zinc.

The nutritional requirement for zinc in the proliferation of normal and malignant cells has been demonstrated in a number of animal studies. A distinction is made between the effect of zinc status upon the host during carcinogenesis and tumor growth. The present studies focus on the Ehrlich ascites tumor in mice fed a semipurified zinc-deficient diet along with defined concentration of zinc in the drinking water.

Early reactions of cadmium with Ehrlich cells.

Ehrlich ascites tumor cells accumulate cadmium against a concentration gradient in a bisphasic uptake process. There is little efflux of the metal from preloaded cells into a cadmium-free medium. Incorporation of 3H-thymidine into DNA is markedly inhibited by cadmium ion at 5-100 ng atoms of Cd/mg of cell protein, but uptake of the nucleoside label into cells is not depressed in this concentration range.

Reactions of 3-ethoxy-2-oxobutyraldehyde bis(N4-dimethylthiosemicarbazonato) cadmium with tumor cells.

The cytotoxic properties of a bis(thiosemicarbazonato) cadmium complex are studied. Preincubation of Ehrlich cells with the complex prevents growth of the ascites tumor in mice. Although the complex inhibits tumor growth without undue initial toxocity, longer-term side effects limit the use of the compound.

Structure-function correlations in the reaction of bis(thiosemicarbazonato) copper(II) complexes with Ehrlich ascites tumor cells.

Examination of a series of substituted bis(thiosemicarbazonato) copper(II) complexes shows that their reaction with Ehrlich ascites tumor cells can be understood in terms of the relative reactivity of the complexes with sulfhydryl groups. In general, the order of reactivity of the complexes correlates directly with their respective degrees of cytotoxicity and ability to inhibit DNA synthesis and cellular respiration. The parent complex, 3-ethoxy-2-oxobutyraldehyde bis(thiosemicarbazonato) copper(II), leads to widespread cellular effects with the suppression of DNA synthesis particularly sensitive to the complex.

Nuclear magnetic resonance studies of cancer. VI. Relationship among spin-lattice relaxation times, growth rate, and water content of Morris hepatomas.

Relaxation time(s) (T1), growth rates, and the water content of six Morris hepatomas, several murine tumors, and a selection of normal tissues indicated that malignant tumors did not always exhibit longer T1 values than any normal tissue, as previously suspected. This overlap raised the possibility of confusion between normal and malignant tissues studied by this method. Tissue T1 values depended primarily on the hydration of the tissue and correlated well with water content determinations.

Nuclear magnetic resonance investigations of human neoplastic and abnormal nonneoplastic tissues.

A large number of samples of human neoplastic and abnormal nonneoplastic tissues were studied by nuclear magnetic resonance spectrometry in order to evaluate the possible role of this technique in the diagnosis of cancer. The spin-lattice magnetic relaxation times (T1) of abnormal nonneoplastic tissue were longer, in many instances, than those of malignant tumors from similar sites, preventing recognition of the tumors in this manner. The evidence for the nonspecific nature of the prolongation of T1 in abnormal tissue is reviewed, and additional limitations of this technique in the diagnosis of cancer are indicated.