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Biomedical subjects

W E Antholine

Publications and source records attributed to W E Antholine.

85 records · Page 5Linked to original sources
PubMed1981

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) . poly(dA-dT) via its bithiazole group to change the environment of the Fe2+ ion. Glutathione binds to the CO-Fe(II)Blm-poly(dA-dT) . poly(dA-dT) complex under conditions in which it stimulates DNA strand scission by Fe(II)Blm.

Bleomycin↗
PubMed1980

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. With Blm and CuBlm there was no obvious relationship between cytotoxicity and the modest short-term inhibition of DNA synthesis by the drugs. The antitumor experiments produced qualitatively similar results with the order of antitumor potency being CuBlm > Blm > ZnBlm approximately equal to FeBlm > CoBlm approximately equal to control tumor. The host toxicity produced by these drugs as measured by weight loss had the opposite ordering: CoBlm < FeBlm < ZnBlm < Blm < CuBlm. At therapeutically effective concentrations, FeFlm was significantly less toxic relative to ther other active agents.

Animals↗
PubMed1979

Paramagnetic changes during development of DMBA-induced mammary tumours in Sprague-Dawley rats.

Paramagnetic changes occurring during development of mammary tumours in Sprague--Dawley rats induced by the chemical DMBA were studied using electron spin resonance. A two-fold increase in free-radical signal intensity was observed at the time of appearance of the tumour. The free radical concentration remained elevated to this level throughout the experiment. This change is different from the gradual decrease reported for frozen ESR samples in other experimental tumour systems and from the pattern reported for lyophilised samples. A gradual increase in the concentration of Mn2+ was also observed. A high frequency (35 GHz) ESR spectrometer was used which enabled us to study the small amount of tissue available from small tumours and normal breast tissue. Quantitative histological analysis of the samples after ESR study indicated that the ESR signal in the normal tissues could not be attributed to any particular cell type, including glandular cells. The increase observed in the tumour appeared to be due to an increased concentration of paramagnetic species in the tumour cells. Most of the tumours were adenocarcinomas but several benign adenomas were also observed. The ESR signals in the benign tumours were indistinguishable from those of the malignant tumours.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1976

Inhibition of tumor cell transplantability by iron and copper complexes of 5-substituted 2-formylpyridine thiosemicarbazones.

The cytotoxicity of copper and iron complexes of 5-substituted 2-formylpyridine thiosemicarbazones against Ehrlich ascites tumor cells has been measured. Brief in vitro incubation of cells and drugs is followed by implantation into host mice. Subsequent degree of tumor development is a measure of cytotoxicity. A spectrum of activities for the iron complexes is observed, starting with the least active as designated by its 5-substitution: OH less than OCOCH3 approximately N(CH3)2 less than H less than CH3 approximately Cl approximately CF3. The last three complexes can prevent completely tumor growth in the new host. Copper complexes of 5-H and 5-CH3 also prevent successful tumor cell transplantation.

Animals↗
PubMed1975

Nitrosylhemoglobin Wood: effects of inositol hexaphosphate on thiol reactivity and electron paramagnetic resonance spectrum.

Properties of Hb Wood (beta-97(FG4)His leads to Leu), a high oxygen affinity hemoglobin with reduced hemeheme interaction, were examined in its nitric oxide liganded form. The reactivity of the beta-93 thiol groups and the electron paramagnetic resonance (EPR) spectrum were examined to determine what effect the amino acid substitution, which occurs at the alpha1beta2 interface, would have on inositol hexaphosphate induced transition of this form of the tetramer. Binding of inositol hexaphosphate (IHP) in a 1:1 stoichiometry was demonstrated. In spite of apparently normal interaction with IHP, there was little or no change in the reactivity of the beta-93 thiol groups and in the electron paramagnetic resonance (EPR) spectrum as contrasted with the marked changes characteristic of normal hemoglobin (HbA). In contrast with NO-HbA, there was also no development of the EPR hyperfine structure in NO-Hb Wood with increased protonation of the protein at pH below 7.0. Taken together with the observations of Henry and Banerjee ((1973), J. Mol. Biol. 73, 469) on the development of NO-Hb EPR hyperfine structure and of Perutz et al. (1974a), Biochemistry 13, 2174) on changes in thiol reactivity with the R leads to T transition, the results suggest that IHP or H+ cannot switch NO-Hb Wood to the T conformation. Since the atomic structures of met- and deoxyhemoglobin offer no indication that His-97 plays any special part in the allosteric mechanism (M. E. Perutz, personal communication), it appears that the replacement of His-97 by Leu reduces the stability of the T structure relative to that of R.

Binding Sites↗