Magnetic ground states of CaRu(1-x)Mn(x)O(3)(0.2 ≤ x ≤ 0.9): a magnetic Compton scattering study.

The magnetism of CaRu(1-x)Mn(x)O(3)(0.2≤x≤0.9) was studied by the magnetic Compton scattering experiment. The result of the spin-polarized electron momentum density distributions (magnetic Compton profiles) and the absolute value of spin moment indicate that Mn doping introduces magnetic moments on Ru ions, and the Ru and Mn spin moments were antiferromagnetically coupled. Moreover the spin moment of Ru ions increased proportionally in the x range. These results were explained by a mixed valence model and inhomogeneous magnetic structure, where the inhomogeneous magnetic ground state in CaRu(1-x)Mn(x)O(3) would be formed by a ferrimagnetic network from the Mn(3.5+) and Ru(4.5+) clusters in the paramagnetic matrix CaRuO(3) for x<0.5 and in the antiferromagnetic matrix CaMnO(3) for x>0.5.

Ferromagnetism in CaMn(1-x)Ir(x)O(3).

The crystallographic, magnetic, and electric properties of CaMn(1-x)Ir(x)O(3) (0≤x≤0.6) were investigated. The lattice constants increase with increasing content of Ir. Specimens of 0.05≤x≤0.2 show antiferromagnetic behavior; however, ferromagnetism is observed for specimens of 0.3≤x≤0.6. T(N) decreases as the Ir content increases. T(N) is superseded by T(C) without passing 0 K and T(C) continues to increase in the ferromagnetic composition range. The effective moment µ(eff) decreases as the Ir content increases. The Weiss temperature is negative for small x; however, it continues to increase while changing its sign at about x = 0.3. The results were explained by assuming a mixed valence state of Mn(3+), Mn(4+), Ir(4+), and Ir(5+) ions. The composition dependence of µ(eff) could be explained qualitatively using the ion fractions estimated from the Ir content dependence of the unit cell volume. Experimental results suggest the coexistence of antiferromagnetic and ferromagnetic phases. When the volume fraction of the ferromagnetic phase dominates that of the antiferromagnetic phase, the system seems to show ferromagnetism.

Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced induction in Epstein-Barr virus early antigen in Raji cells.

Retinol, 5 flavonoids, 3 steroids and 7 sweetening agents were studied for their effects on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced early antigen (EA) of Epstein-Barr virus (EBV) in Raji cells. Concomitant treatment of Raji cells with TPA and retinol showed inhibition of EA induction. Among flavonoids, quercetin resulted in effective inhibition of EA induction by TPA and alpha-naphthoflavone showed the weakly inhibitory effect. None of the other flavonoids such as rutin, catechin and beta-naphthoflavone affected the induction of EBV-EA by TPA. beta-Estradiol obviously inhibited EBV-EA induction by TPA, but hydrocortisone did not show any inhibitory effect on it. Glycyrrhetinic acid, steviol, phyllodulcin and perrillartine also showed the remarkable inhibition of EBV-EA induction. On the other hand, glycyrrhizin and stevioside, glycosides of glycyrrhetinic acid and steviol, did not inhibit the induction of EBV-EA by TPA. Some of the inhibitors reported here may be effective on the inhibition of the in vivo tumor promotion by TPA.

Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced induction of Epstein-Barr virus early antigen in Raji cells by some inhibitors of tumor promotion.

The effects of some compounds, which have been reported to inhibit tumor promotion in vivo, on the induction of the early antigen (EA) of Epstein-Barr virus (EBV) by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells were examined. The inhibitors of the cascade process involving arachidonic acid, indomethacin, nordihydroguaiaretic acid, phenidone and p-bromophenacyl bromide, effectively inhibited EBV-EA induction by TPA. Two flavonoids, morin and kaempferol also inhibited EA induction. Among antioxidants, butylated hydroxytoluene effectively inhibited EA induction, though alpha-tocopherol did not show any inhibition of EA induction at concentrations of up to 150 micrograms/ml. N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide, a calmodulin antagonist, and esculetin showed inhibitory effects on EA induction, though slight cytotoxicity was observed. L-1-p-Tosylamino-2-phenylethyl chloromethyl ketone, a protease inhibitor, showed cytotoxicity and no specific inhibition of EA induction. Five kinds of steroids, cortisone, hydrocortisone, prednisolone, dexamethasone and fluocinolone acetonide showed no inhibitory effect on EA induction at concentrations of up to 100 micrograms/ml. In addition, the relationship between the inhibition of EBV-EA induction and that of tumor promotion is discussed.

Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced ornithine decarboxylase activity in mouse epidermis by sweetening agents and related compounds.

The effects of naturally occurring sweetening agents, which inhibited the induction of Epstein-Barr virus-associated early antigen (EBV-EA) induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), and related compounds on the induction of ornithine decarboxylase (ODC) by TPA is examined. Application of glycyrrhetinic acid or steviol to mouse skin 1 h before TPA treatment showed a remarkable decrease in TPA-induced ODC activity. Post-treatment with glycyrrhetinic acid or steviol 1 h after application of TPA also resulted in a considerable depression in the induction of ODC activity. Neither glycyrrhetinic acid nor steviol alone induced epidermal ODC activity. These results suggest that glycyrrhetinic acid and steviol interfere with the process of induction of epidermal ODC by TPA treatment of mouse skin. cis-Abienol, frullanolide and norambreinolide, which have a partially similar structure in the moiety with glycyrrhetinic acid or steviol, were tested. cis-Abienol and frullanolide showed an inhibitory effect when applied 1 h before TPA treatment, but norambreinolide was not effective. A relationship between suppression of ODC activity and inhibition of EBV-EA induction is discussed.

Formation of mutagens by heating foods and model systems.

We have demonstrated that the pyrolysis products of amino acids and proteins in model systems are mutagenic. The mutagenic principles in the pyrolyzates of amino acids have been isolated and identified by Sugimura et al. We have isolated and identified amino-alpha-carbolines from pyrolyzed soybean globulin as mutagens. The yield of mutagens by the heating of food constituents is changed by the heating method. Effects of heating methods on the yield of amino-alpha-carbolines were studied in a series of experiments, and the results are shown in this paper. Additionally, it has been shown that by the heating of creatine-sugar mixtures imidazoquinoline or quinoxaline mutagens are formed.

Mutagenicity of polycyclic aromatic hydrocarbons and quinones on Salmonella typhimurium TA97.

18 polycyclic aromatic hydrocarbons (PAHs) and 7 quinones were tested for mutagenicity using Salmonella typhimurium TA97, TA98 and TA100 with or without metabolic activation. In the presence of metabolic activation, TA97 was more susceptible to mutation than either TA98 or TA100 by many of PAHs tested. PAHs such as 1-methylphenanthrene, fluoranthene, pyrene, benzo[a]pyrene, benzo[e]pyrene and perylene had high mutagenic effects on TA97 in the presence of metabolic activation. 1,6- and 1,8-pyrenequinones were also highly mutagenic on TA97 in the presence or absence of metabolic activation. It appears that pyrene is mutagenic through its metabolic conversion to pyrenequinones.

Factors affecting mutagenic activity of cigarette smoke condensate in Salmonella typhimurium TA 1538.

Smoke condensates from Burley tobacco, bright-type tobacco and various brands of commercial cigarettes were tested for mutagenicity by using a microsomal test system with Salmonella typhimurium TA 1538. Smoke condensate from Burley tobacco had much higher mutagenic activity than that from bright-type tobacco. Increased mutagenic activity was observed with smoke condensates from Burley tobacco grown with increasing amounts of nitrogen fertilizer, and from commercial cigarettes blended with Burley tobacco. There was a significant correlation between nitrate content of cigarette and mutagenic activity of the resulting smoke condensate. The results suggest that nitrate in cigarettes may influence the formation of potential mutagens during the burning of a cigarette.

Mutagenic activity of amino acid pyrolyzates in Salmonella typhimurium TA 98.

Pyrolyzates of 25 amino acids and 5 indole derivatives were tested for mutagenicity in the histidine-requiring mutant Salmonella typhimurium TA 98. Significant mutagenic activity was detected with pyrolyzates of most of the amino acids. These pyrolyzates required a liver microsomal fraction, as representative of mammalian metabolism, to be detected as mutagens. Among the pyrolyzates tested, the highest mutagenic activity was observed with that of L-tryptophan. As little as 10 microgram of the pyrolyzate of L-tryptophan had detectable mutagenic activity toward TA 98. The optimal pyrolysis temperatures for the formation of mutagenic products were shown to be 500 degrees C for L-tryptophan and 600 degrees C for the other amino acids. The results from pyrolyses of some indole derivatives suggest that an amino group at the alpha-position to the carboxyl group of L-tryptophan plays an important role in the formation of mutagens.

Relation between chemical constituents of tobacco and mutagenic activity of cigarette smoke condensate.

Mutagenic activities of cigarette smoke condensate were assayed in the presence of S-9 Mix using Salmonella typhimurium TA 98. The results were examined in relation to chemical data of tobacco leaves. Among the nitrogenous constituents examined, the contents of total nitrogen and protein nitrogen and the soluble nitrogenous fraction were positively and significantly related to an increase in mutagenic activity of the smoke condensate, whereas nicotine and nitrate were not important in contributing to mutagenic potency of such condensates. The age of tobacco leaves influenced the mutagenic potency of the condensate, which was lowest in leaves from the lower stalk position and increased with ascending leaf position on the stalk. Smoke condensate from tobacco with higher sugar content resulted in lower mutagenic activity. The present results, together with the previous study on the mutagenicity of the amino acid pyrolyzates, suggest that potent mutagens in cigarette smoke condensate are nitrogen-containing compounds, which may be formed from proteins and amino acids during the burning of a cigarette.

Mutagenicities of the pyrolyzates of peptides and proteins.

Pyrolyzates of 10 peptides, 10 proteins and 5 naturally-occurring materials were tested for mutagenicity in the histidine-requiring mutants Salmonella typhimurium TA98 and TA100. Significant mutagenic activity was detected with pyrolyzates of most of these materials. The pyrolyzates requred a liver microsomal fraction, as representative of mammalian metabolism, for their detection as mutagens. Among the pyrolyzates tested, the highest mutagenic activity was observed with that of a tryptophan-containing peptide. The pyrolyzate of protein obtained from tobacco leaf also showed mutagenicity. The higher the protein content in the leaf the higher the mutagenic activity of the pyrolyzate. Protein in a tobacco leaf may be the principal precursor of mutagens in tobacco-smoke condensate.

The role of 3d electrons in the appearance of ferromagnetism in the antiferromagnetic Ru2MnGe Heusler compound: a magnetic Compton scattering study.

The antiferromagnetism in Ru(2)MnGe can be suppressed by the substitution of V by Mn and ferromagnetism appears. Synchrotron-based magnetic Compton scattering experiments are used in order to investigates the role of 3d electrons in the indirect/direct exchange interactions for the appearance of ferromagnetism. A small spin moment for the itinerant electron part on the magnetic Compton profile indicates that the metallic ferromagnet Ru(2)Mn(0.5)V(0.5)Ge has a weak indirect exchange interaction between the d-like and sp-like (itinerant) electrons. This suggests that the appearance of ferromagnetism is caused by the enhancement of the direct exchange interactions between d-d electrons in the Ru(2)MnGe Heusler compound. These findings indicate that the indirect exchange interaction between itinerant electrons and localized electrons is a significant key point for the appearance of ferromagnetism in this system.

Variation of the Ru moment in the Ca(0.3)Sr(0.7)Ru(1-x)Mn(x)O3 system.

The variation of the magnetic moment on Ru and Mn atoms in the Ca(0.3)Sr(0.7)Ru(1-x)Mn(x)O(3) system was investigated by the magnetic Compton scattering technique using synchrotron radiation. The Ca(0.3)Sr(0.7)Ru(1-x)Mn(x)O(3) system has ferrimagnetism with an antiferromagnetic coupling between Ru and Mn, and the dominant magnetic component changes from ferromagnetic Ru to ferromagnetic Mn at x ∼0.25 as the Mn substitution proceeds. The mechanism for the change in the magnetism of Ca(0.3)Sr(0.7)Ru(1-x)Mn(x)O(3) is discussed.

Orbital magnetic moment in Ir doped CaMnO(3).

The magnetism of CaMn(0.55)Ir(0.45)O(3) has been studied using the magnetic Compton scattering technique. The analysis of the magnetic Compton profile shows that the spin moments of Mn and Ir form an antiparallel configuration, establishing ferrimagnetism. Moreover, the experimental results indicate the existence of an orbital moment 0.2  µ(B)/f.u.. The possible model for these results has been discussed under the framework of the localized electron model by taking account of the electronic states of the Ir(4+) ion.

Caffeine inhibition of the metabolic activation of a carcinogen, 4-nitroquinoline-1-oxide, in cultured Chinese hamster cells.

The cytotoxic effect of 4-nitroquinoline-1-oxide (4NQO) on cultured Chinese hamster cells was drastically reduced by the presence of caffeine (0.2-1 mM). Caffeine, however, did not reduce the cytotoxicity of 4-hydroxyaminoquinoline-1-oxide (4HAQO), an active metabolite of 4NQO. The 105 000 g supernatant from the cell homogenate could catalyze the conversion of 4NQO to 4HAQO in the presence of NADPH or NADH as a hydrogen donor. This enzyme activity was strongly inhibited by caffeine (0.1-10 mM) or dicumarol (10(-8)-10(-6) M), an inhibitor of DT diaphorase (E.C.1.6.99.2). Dicumarol also reduced the cytotoxicity of 4NQO. These results clearly suggest that caffeine inhibits the conversion step of 4NQO to 4HAQO, resulting in a decrease in the cytotoxicity of 4NQO. Furthermore, the frequency of 6-thioguanine-resistant mutation by 4NQO was also strongly reduced by the presence of caffeine (1 mM) in cultured Chinese hamster cells, being consistent with the results of cytotoxicity.

Phytochemical Studies on the Tobacco Alkaloids. XII. Identification of gamma-Methylaminobutyraldehyde and its Precursor Role in Nicotine Biosynthesis.

gamma-Methylaminobutyraldehyde (N-methylpyrroline) labeled with (14)C was isolated from tobacco roots which had metabolized ornithine-2-(14)C. It was labeled most strongly 4 hours after adding ornithine-2-(14)C to the root, also labeled by putrescine-1,4-(14)C and methionine-(14)CH(3), and observed in the root but not in the aerial portions of tobacco plants. gamma-Methyl-aminobutyraldehyde when added back to the root was an efficient precursor of nicotine. Identity of gamma-methylaminobutyraldehyde from tobacco roots was confirmed by comparison with the authentic compound.The existence of gamma-methylaminobutyraldehyde (N-methylpyrroline) in the biosynthetic pathway of nicotine indicates that the methyl group must be introduced before condensation of the pyridine moiety with the pyrrolidine moiety.

Identification of cembratriene-4,6-diol as antitumor-promoting agent from cigarette smoke condensate.

Cigarette smoke condensate (CSC) was separated into several fractions and each was tested for an inhibitory effect on the early antigen (EA) of Epstein-Barr virus (EBV) which can be induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. Two diastereoisomers of 2,7,11-cembratriene-4,6-diol (alpha- and beta-CBT) were isolated from the neutral fractions of CSC and these showed potent inhibitory effects on the induction of EBV-EA by TPA. The doses of alpha- and beta-CBT required for 50% inhibition of EBV-EA induction by TPA were 7.7 and 6.7 micrograms/ml, respectively, which are comparable with those of retinoic acid, a potent inhibitor of induction of epidermal ornithine decarboxylase (ODC) activity and tumor promotion by TPA in mice. Application of alpha- and beta-CBT to mouse skin prior to treatment with TPA inhibited TPA-induced ODC activity. The degree of inhibition was dependent on the dose and application of 16.5 mumol/mouse of alpha- and beta-CBT resulted in a 50 and 40% reduction, respectively, of the maximum of the ODC activity induced as a result of treatment with TPA. In initiation-promotion experiments, alpha-CBT markedly inhibited the promoting effect of TPA on skin tumor formation in mice which were initiated with 7,12-dimethylbenz[a]anthracene, but beta-CBT was found to be less effective. Application of 3.3 mumol of alpha-CBT 40 min prior to treatment with TPA (1 microgram) resulted in a 53% reduction in the number of papillomas per mouse. Our present data suggest that EBV-EA inhibition assay using Raji cells is effective for the first screening of inhibitors of tumor promotion, and provide evidence that CSC contains antitumor-promoting agents in addition to carcinogenic and tumor-promoting agents already reported.

Inhibition of 12-O-tetradecanoylphorbol-13-acetate-stimulated 32Pi incorporation into phospholipids and protein phosphorylation by 2,7,11-cembratriene-4,6-diol, an antitumor-promoting agent.

A possible mechanism of antitumor-promoting activity of alpha-2,7,11-cembratriene-4,6-diol (alpha-CBT) was studied. alpha-CBT inhibited the 32Pi incorporation into phospholipids of HeLa cells stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA). In contrast to the property to interact with calmodulin of many other antitumor-promoting agents, which were proved to inhibit TPA-stimulated 32Pi incorporation into phospholipids, alpha-CBT did not show any interaction with calmodulin; i.e., the fluorescence of N-phenyl-1-naphthylamine enhanced by binding with Ca2+-calmodulin was not influenced by treatment with alpha-CBT. TPA-stimulated phosphorylation of 47-kilodalton protein, which is phosphorylated by protein kinase C in human platelets, was found to be inhibited by alpha-CBT. However, the specific binding of 3H-TPA to mouse epidermal particulate fraction was not inhibited by treatment with alpha-CBT. These results suggest that alpha-CBT inhibits the activity of protein kinase C by another mode of action rather than the effect on its receptor site, and that this action and calmodulin-independent inhibitory effect on phospholipid metabolism of alpha-CBT may play a certain role in its antitumor-promoting activity in vivo.