Relative biological effectiveness (RBE) of low-dose californium-252

Relative biological effectiveness (RBE) of 252Cf, with respect to 192Ir, has been determined at the low dose rates commonly used in interstitial and intracavitary therapy. The biological criterion was growth reduction in Vicia faba bean roots. Two varieties of Vicia faba were used. For Vicia faba Sutton's seeds, an RBE of 5.7 to 6.6 was obtained for 252Cf Dn + gamma doses of 0.5 to 0.2 Gy respectively and at a Dn + gamma dose rate of 0.11 Gy-1. The gamma contribution D gamma/Dn + gamma at the level of the root tipes was 0.35 and the derived RBE of the neutron emission of 252Cf was then 8.2 to 9.7. For Vicia faba Be1B and in the same irradiation conditions, an RBE of 5.1 to 6.2 was obtained for the total (n + gamma) 252Cf emission and for Dn + gamma doses of 0.4 to 0.2 Gy respectively. These values lead to an RBE of 7.4 to 9.0 for the neutron emission of 252Cf. For Vicia faba BelB, but for another source arrangement (Dn + gamma dose rate of 0.13 Gy . h-1 for 252Cf), an RBE of 5.6 to 7.5 was obtained for the total (n + gamma) emission of 252Cf and for Dn + gamma doses of 0.4 to 0.1 Gy respectively. The gamma contribution (D gamma/Dn + gamma) at the level of the root tips was 0.42, and the derived RBE of the neutron emission of 252Cf was then 8.9-12.3.     

Sperm shape abnormalities in mice exposed to californium-252 radiation

Male mice of the B6C3F1 hybrid strain were whole-body irradiated with different doses of 252Cf/60Co. They were killed 35 days later and spermatozoa from cauda epididymides were stained with eosin-Y. The air-dried smears were examined under light microscope for sperm shape abnormalities. There was an increase in the frequency of abnormal sperm in all the treated groups compared to controls. The RBE for the mixed neutron and gamma radiation of 252Cf was 2.6. The RBE for the neutron component was 3.4. The increased frequency of abnormal sperm was associated with a concomitant decrease in testis weight in the irradiated animals.     

Synthesis and biological activity of pyrazole analogues of the staurosporine aglycon K252c

A derivative of the staurosporine aglycon (K252c), in which the lactam ring was replaced by a pyrazole moiety, was synthesized. The resulting indolopyrazolocarbazole (3) inhibited Pim isoforms 1–3 whereas it did not impair the activity of two known targets of K252c, protein kinase C isoforms α and γ. Compound 3 exhibited moderate cytotoxic activity toward human leukemia and colon carcinoma cell lines (K562 and HCT116), strongly suggesting that this new scaffold deserves further investigations for treatment of malignancies associated with Pim activity.     

Study of the interaction of triethylenethiophosphamide with nucleotides by mass spectrometry with ionization by fission fragments of californium-252]

Study of interaction of the antitumor alkylating drug triethylenethiophosphoramide (thioTEPA) with nucleotides (dGMP and dCMP) suggests highly perspective employment of 252-Cf fission fragment induced desorption mass spectrometry (252-Cf PDMS) in biochemical pharmacology. Using the 252-Cf PDMS the molecular masses of the unstable, unvolatile, high-molecular substances of biological origin and the chemical adducts or complexes with drugs can be used to establish some structural-functional parameters of the above mentioned biomolecules and their derivatives in microvolumes of the incubation medium. The resulting data may be used for modelling chemotherapeutic processes of "drug-biomolecule-target" type. Using 252-Cf PDMS the complexes (dGMP (thioTEPA) n), n = 1, 2, 3 and (dCMP (thioTEPA) n), n = 1, were obtained. Some quantitative parameters and stability of these complexes were studied. Binding of dGMP with drug in the presence of dCMP was shown preferential. The data are compatible with the predictions concerning the mechanism of the antitumor property of the thioTEPA which can be manifested in the impairment structure of DNA of the malignant cells.     

Survival of clonogenic cells of Lewis lung carcinoma cells forming colonies in agar cultures in diffusion chambers during gamma-irradiation and exposure to gamma-neutron californium-252 irradiation

Clonogenic cells forming colonies in agar cultures in diffusion chambers and those isolated from subcutaneously transplanted Lewis lung carcinoma do not differ in their sensitivity to 60Co gamma-rays with respect to tumor growth stages. The dose-survival curves for all studied cells are S-shaped with a small shoulder. A cumulative dose-survival curve for malignant clonogenic cells is characterized by the average value of mean lethal dose D0 = 2.24 Gy and extrapolation number n = 2.0. When exposed to gamma-neutron-radiation (252Cf) malignant clonogenic cells exhibit a nearly exponential dose-survival curve with D0 = 0.56 Gy (with respect to a neutron component). The RBE of gamma-neutron radiation (252Cf) is 2.5.     

A radiobiological model for the relative biological effectiveness of high-dose-rate 252Cf brachytherapy

While there is significant clinical experience using both low- and high-dose-rate 252Cf brachytherapy, there are minimal data regarding values for the neutron relative biological effectiveness (RBE) with both modalities. The aim of this research was to derive a radiobiological model for 252Cf neutron RBE and to compare these results with neutron RBE values used clinically in Russia. The linear-quadratic (LQ) model was used as the basis to characterize cell survival after irradiation, with identical cell killing rates (S(N) = S(gamma)) between 252Cf neutrons and photons used for derivation of RBE. Using this equality, a relationship among neutron dose and LQ radiobiological parameter (i.e., alpha(N), beta(N), alpha(gamma), beta(gamma)) was obtained without the need to specify the photon dose. These results were used to derive the 252Cf neutron RBE, which was then compared with Russian neutron RBE values. The 252Cf neutron RBE was determined after incorporating the LQ radiobiological parameters obtained from cell survival studies with fast neutrons and teletherapy photons. For single-fraction high-dose-rate neutron doses of 0.5, 1.0, 1.5 and 2.0 Gy, the total biologically equivalent doses were 1.8, 3.4, 4.7 and 6.0 RBE Gy with 252Cf neutron RBE values of 3.2, 2.9, 2.7 and 2.5, respectively. Using clinical data for late-responding reactions from 252Cf, Russian investigators created an empirical model that predicted high-dose-rate 252Cf neutron RBE values ranging from 3.6 to 2.9 for similar doses and fractionation schemes and observed that 252Cf neutron RBE increases with the number of treatment fractions. Using these relationships, our results were in general concordance with high-dose-rate 252Cf RBE values obtained from Russian clinical experience.     

Synthesis and biological activity of dialkylphosphocholines

A series of dialkylphosphocholines were prepared and evaluated for their biological activity. The antiprotozoal activity was determined against Acanthamoeba lugdunensis. Compound 15 exhibited excellent trophocidal activity. None of the tested dialkylphosphocholines exhibited better fungicidal activity against Candida albicans than miltefosine. The antineoplastic activity was determined against HeLa. The most cytotoxic was compound 10, which was more active against tumor cells as against normal cells.     

Syntheses and biological activity of bisdaunorubicins

To study the length and flexibility of the linkers between two monomers of bisdaunorubicins for their activity against cancer cells, seven bisdaunorubicins were rationally designed and synthesized through click chemistry. Their cytotoxicity was tested in leukemia cells with MTS assay. The results showed that the compounds with short linkers exhibited higher activity than the compounds with long linkers, while the flexibility of the linker also contributed to their activity. These results indicated that the length and flexibility of the linkers between two monomers in bisdaunorubicins are very critical to maintain their activity against cancer cells.     

Antioxidant and biological activity of melatonin

Neurohormone melatonin controls the circadian rhytmicity of some biological processes, unites the functions of nervous, endocrine and immune systems. Melatonin is a powerful bioantioxidant, capable to be dissolved in water and lipids, runs through membranes and barriers, accumulates in cell nuclei and protects DNA from oxidative stress. Melatonin displays immunomodulating, radioprotective and antitumor activities.     

Isolation and biological activity of frankiamide

An antibiotic produced by the symbiotic actinomycete Frankia strain AiPs1 was isolated from culture broth using optimized thin-layer chromatography and high-performance liquid chromatography (HPLC) methods. The novel compound that was isolated, dubbed frankiamide, displayed antimicrobial activity against all 14 Gram-positive bacterial strains and six pathogenic fungal strains tested. The pathogenic actinomycete Clavibacter michiganensis and the ooymycete Phytophthora were especially susceptible. In addition to displaying antimicrobial activity, frankiamide also strongly inhibited ⁴⁵Ca²⁺ fluxes in clonal rat pituitary GH₄C₁ tumor cells and was comparable to a frequently used calcium antagonist, verapamil hydrochloride. The results of HPLC analysis, supported by both nuclear magnetic resonance and mass spectroscopy studies, showed that frankiamide has a high affinity for Na⁺ ions. Journal of Industrial Microbiology & Biotechnology (2001) 27, 62–66. Received 26 February 2001/ Accepted in revised form 01 June 2001     

Methylglyoxal: metabolism and biological activity

The enzymic formation of methylglyoxal from dihydroxyacetone phosphate and aminoacetone (metabolites of carbohydrates and proteins) is considered. Methylglyoxal transformation into lactic and pyruvic acids is related to energy metabolism, catabolism and anabolism dissociation processes in carbohydrates and proteins, and, probably, to maintenance of asymmetrical entropy in vivo on the constant level. Attention is paid to the methylglyoxal inhibition of enzymes, its interaction with glutathione and polyamines affecting the mechanisms regulating protein synthesis and cellular division. The methods for obtaining and quantitative determination of methylglyoxal are described.     

Natural phenanthrenes and their biological activity

The aim of this review is to survey the various naturally occurring phenanthrene compounds that have been isolated from different plants. Only one review has previously been published on this topic. Gorham (1989) reviewed the structures, biosynthesis, separations and spectroscopy of stilbenes and phenanthrenes. The present study furnishes an overview of the hydroxy or/and methoxy-substituted 9,10-dihydro/phenanthrenes, methylated, prenylated and other monomeric derivatives, dimeric and trimeric phenanthrenes and their biological activities. A fairly large number of phenanthrenes have been reported from higher plants, mainly in the Orchidaceae family, in the species Dendrobium, Bulbophyllum, Eria, Maxillaria, Bletilla, Coelogyna, Cymbidium, Ephemerantha and Epidendrum. A few phenanthrenes have been found in the Hepaticae class and Dioscoreaceae, Combretaceae and Betulaceae families. Their distribution correlates strongly with the taxonomic divisions. These plants have often been used in traditional medicine, and phenanthrenes have therefore been studied for their cytotoxicity, antimicrobial, spasmolytic, anti-inflammatory, antiplatelet aggregation, antiallergic activities and phytotoxicity. On the basis of 120 references, this review covers the phytochemistry and pharmacology of phenanthrenes, describing 252 compounds. This contribution stems from our work on the medicinal plant Tamus communis.     

New azidometalkojates and their biological activity

Azidometalkojates of the general formula MX₂ (M=Cu, Mn, Mg, Zn or Ni and X=5-hydroxy-2-azidomethyl-4H-pyran-4-one) were prepared and tested for antibacterial, antifungal and cytotoxic effects. The mangan and zinc derivatives are not active against any the tested microorganisms. A weak antibacterial activity was found with the copper derivative. The strongest antifungal effects were shown by the nickel derivative while the highest cytotoxic effect on HeLa cells was manifested by the zinc derivative.     

Yersinia lipopolysaccharide and its biological activity

The data on the structure and biological activity of the lipopolysaccharide (LPS) of Yersinia as an important virulence factor are analyzed. The biological effects of LPS are characterized by dose dependence: small doses stimulate the intensity of phagocytosis, while large doses decrease phagocytic activity and produce cytotoxic effect. Yersinia LPS plays an important role in the development of such consequences of yersiniosis as reactive arthritis, erythema nodosum, Reiter's syndrome. Yersinia LPS is a widespread component for the diagnostics of yersiniosis and pseudotuberculosis.     

Luteolytic prostaglandins synthesis and biological activity

Analogues of PGF_2α with enhanced luteolytic activity were synthesized using the Corey synthesis. The luteolytic activity of the new prostaglandins was tested in the hamster.In addition the smooth muscle activity of the new compounds was compared with that of PGA₂ on the longitudinal strip of rat stomach fundus. Structure-activity relationships in the new series of 17,18,19,20-tetranor-16-thienyl-oxy-PGF_2α are discussed.     

Aspartic acid 252 and asparagine 185 are essential for activity of lipid N-acetylglucosaminylphosphate transferase

A key step in the assembly of oligosaccharide-lipid intermediatesin N-linked glycosylation is the transfer of N-acetylglucosamine1-phosphate to dolichyl phosphate, catalyzed by the enzyme UDP-N-acetylglucosaminyl:dolichylphosphate N-acetylglucosaminyl phosphoryl transferase (L-G1PT).Comparison of the amino acid sequences of L-G1PT from five diversespecies showed 75 amino acids identical in all five proteins.Using site-directed mutagen-esis, we analyzed the importanceof a number of these conserved residues to the enzymatic activityof L-G1PT using a plasmid shuffling procedure in Schizosaccharomycespombe. S.pombe cells containing a chromosomal deletion of theessential gpt⁺ gene are rescued by a plasmid containing theS.pombe gpt open reading frame. Replacement of that plasmidby a plasmid encoding a mutated hamster L-G1PT cDNA sequenceindicated that the mutated protein provided sufficient enzymeactivity to permit cell growth. Mutations of aspartic acid 252and asparagine 185 did not allow plasmid shuffling, indicatingthese residues were essential for activity. A combination ofmutations at asparagine 182 and tryptophan 122 did not allowplasmid shuffling, although the single mutations did. Overexpressionof the mutant proteins in S.pombe conferred tunicamycin (TM)resistance, indicating that the mutant proteins had a conformationnecessary for binding TM, a substrate analog. The mutant proteinswere also detected in Western blots and were correctly localizedto the membrane fractions. However, the overexpressed proteinsdid not increase the endogenous level of enzymatic activityin these cells, indicating they were enzymatically inactive. N-acetylglucosaminylphosphate transferase mutagenesis plasmid shuffling Schizosaccharomyces pombe tunicamycin