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Transformation of hamster embryo cells by aromatic amines.

a mammalian cell transformation system that required cryopreserved primary cultures of Syrian golden hamster embryo cells was used in the evaluation of the carcinogenic potential of 46 structurally related aromatic amines. The results generally correlated with those obtained with animal bioassay systems. However, several carcinogenic compounds required the addition of an exogenous metabolic activation system provided by hamster liver S9 homogenate enzymes or cultured hepatocytes to transform the hamster embryo cells.

Amines↗

Levels of pollutants and their metabolites: exposures to organic substances.

The measurement of levels of organic pollutants and/or their metabolites in body tissues or fluids are specific markers of internal dose and, provided that the pharmacokinetic properties of the compounds in question are known, these levels may also be used as predictors of effects. Although historical data still remain to be very useful in environmental studies, more reliable exposure measures than combination of environmental levels and such estimators as residential history, job titles, life-style habits, individual perceptions, etc., are highly desirable. This has been clearly demonstrated in studies with 2,3,7,8-tetrachlorndibenzo-p-dioxin (TCDD), where more recent measurements of serum concentrations in persons earlier classified as belonging to exposed groups have indicated that severe misclassifications may have occurred in previously epidemiological studies. This also demonstrates that, in retrospective studies, levels of persistent organic compounds are useful as markers of exposure, as their tissue levels mainly reflect previous exposures. However, most organic compounds are readily metabolized and excreted from the human body, and in many instances it will not be possible with current methodology and instrumentation to detect transient organic pollutants at low levels in the blood. In most cases, the use of urine samples offers a better opportunity to provide samples containing detectable levels. Therefore, the measurement of non-persistent organic substances and/or their metabolites may find potential use in prospective environmental health studies, but the predictive value highly depends on proper timing and frequency of sampling according to their toxicokinetic behaviour. A few examples on the use of organic compounds and/or metabolites as biomarkers are given, e.g., polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs), ochratoxin A, polycyclic aromatic hydrocarbons (PAHs) and cooked food mutagens.

Biomarkers↗

[Triaminotricarboxylic amino acid oxidation productions of actinoidin and ristomycin].

Aromatic acids with three benzene nuclei bound through oxygen were obtained from actinoidin and ristomycin on their oxydation with permanganates of methylated aglycones and peptides. The structures of the methyl esters of these acids were determined by spectral methods. They are the following: methyl-3,5-bis-(4-methoxycarbonyl-phenoxy)-4-methoxybenzoate (from ristomycin) and methyl-3-(2-chlor-4-methoxycarbonyl-phenoxy)-5-(4-methoxycarbonyl-phenoxy)-4-methoxybenzoate (from actinoidin). The compounds are the aromatic parts of the molecules of the unusual triaminotricarboxylic amino acids present in the aglycones of all antibiotics of the group of polycyclic glycopeptides.

Acetylation↗

Compound class specific 14C analysis of polycyclic aromatic hydrocarbons associated with PM10 and PM1.1 aerosols from residential areas of suburban Tokyo.

Compound class specific radiocarbon analysis (CCSRA) was performed for polycyclic aromatic hydrocarbons (PAHs) associated with airborne particulate matter (APM) with diameter <10 microm (PM10) and <1.1 microm (PM1.1) collected from a residential area of suburban Tokyo, Japan, and seasonal and particle-size radiocarbon variations were investigated. Source diagnostic isomer pair ratios indicated mixed contributions from petroleum combustion and from biomass and coal combustion to the PAHs in APM. The delta14C- PAHs in APM, ranging from -787 to -514 per thousand, indicated dominance of fossil fuel combustion. The delta14C of 5-6 rings (HMW) PAHs were higher than the 3-4 rings (LMW) species in both PM10 and PM1.1 samples. The delta14C of HMW-PAHs indicated greater biomass-burning contributions in summer than in winter and no apparent particle-size variation. Conversely, the delta14C of LMW species showed a greater contribution from fossil sources in summer and in larger particles (PM10). This finding could be tentatively attributed to the recondensation of fossil-PAHs vaporized from petroleum sources. A 14C isotopic mass balance approach estimated that biomass burning contributes 17-45% of the PAH burden in suburban Tokyo, and that the increase in the biomass-PAH accounts for approximately 27% and 22% of winter-time elevation of LMW- and HMW-PAHs, respectively. These are far exceeding what is expected from the emission statistics for CO2 and combusted materials in Japan and emphasizing the importance of biomass-burning as a source of PAHs; which, in turn, demonstrates the utility and the significance of field-based source assessment by using CCSRA for an effective regulation of atmospheric pollution by PAHs.

Aerosols↗

[Mass spectrometric studies on dibenzocyclooctadiene lignan compounds from Schisandraceae plants].

Mass spectrometric studies on fragmentation patterns of 23 dibenzocyclooctadiene lignan compounds isolated from Schisandraceae plants, such as schisandra A (1), were carried out by using low and high-resolution mass spectrometric techniques and metastable ion analyses. The main mass spectral characteristics were summarized to provide a sound basis for further researches on Schisandraceae plants and for structural elucidation of similar new compounds.

Chemical Phenomena↗

Chlorobenzylidine-calf thymus DNA interaction II: circular dichroism and nuclear magnetic resonance studies.

The binding of chlorobenzylidine to calf thymus DNA has been studied in detail by means of circular dichroism (CD), nuclear magnetic resonance (1H NMR), viscosimetry and denaturation temperature (Tm). Chlorobenzylidine is found to intercalate between base pairs of DNA as evidence by: (1) induced circular dichroism; (2) broadened 1H NMR signals; (3) enhanced viscosity; and (4) increased denaturation temperature of the DNA helix. In addition, Scatchard plot from CD titration data gives a binding constant of 2.6 x 10(4) M(-1) and a binding site size of 4 base pairs at 25 degrees C. Matrix rank analysis shows that there are three main components contributing to the observed CD spectra. The nuclear magnetic resonance experiment shows that the planar aromatic ring of tetrahydroberberine group in chlorobenzylidine intercalates between the base pairs of DNA when chlorobenzylidine is bound to DNA.

Animals↗

Oxidative biosynthesis of phenylbenzoisochromenones from phenylphenalenones.

13C NMR analysis demonstrated incorporation of two 13C labelled phenylalanine units into phenylphenalenones and phenylbenzoisochromenones co-occurring in Wachendorfia thyrsiflora. These results suggest oxidative formation of phenylbenzoisochromenones following a late branching from a common phenylphenalenone biosynthetic pathway. A dioxygenase-type mechanism, followed by decarboxylation, is suggested for the key steps of this conversion.

Carbon Isotopes↗

Embryotoxic and teratogenic effects of petroleum hydrocarbons in mallards (Anas platyrhynchos).

Egg surface applications of microliter quantities of crude and refined oils of high aromatic content are embryotoxic to mallards (Anas platyrhynchos) and other avian species; applications of aliphatic hydrocarbons have virtually no effect. Mallard eggs at 72 h of development were exposed to a mixture of aromatic hydrocarbons or to aromatic compounds representative to those present in crude oil to assess their toxicity. The class composition of the mixture was similar to that of South Louisiana crude oil, an American Petroleum Institute reference oil. Application of 20 microliter of the mixture reduced embryonic survival by nearly 70%. The temporal pattern of embryonic death was similar to that after exposure to South Louisiana crude oil. Embryonic growth was stunted, as reflected by weight, crown-rump length, and bill length, and there was a significant increase in the incidence of abnormal survivors. When individual classes of aromatic hydrocarbons were tested, tetracyclics caused some embryonic death at the concentrations in the mixture. When classes were tested in all possible combinations of two, no combination appeared to be as toxic as the entire mixture. Addition of the tetracyclic compound chrysene to the aromatic mixture considerably enhanced embryotoxicity, but could not completely account for the toxicity of the crude oil. The presence of additional unidentified polycyclic aromatic hydrocarbons as well as methylated derivatives of polycyclic aromatic compounds such as chrysene may further account for the embryotoxicity of the crude oil.

Animals↗

Effects of Aconitum alkaloid kobusine and pseudokobusine derivatives on cutaneous blood flow in mice.

Aconitum alkaloids of the C20-diterpenoid type, kobusine (1) and pseudokobusine (2), and their acetyl, benzoyl, propionyl or cinnamoyl derivatives are examined for their peripheral vaso-activities by laser-flowmetrical measurement of the cutaneous blood flow in the hind foot of mice after intravenous administration. A dose-relationship of maximally increased blood flow after the administration of either of the Aconitum alkaloids existed. Kobusine 15-acetate (4), 11-benzoate (6) and 15-benzoate (7) were significantly effective at a low dose of 1 mg/kg, whereas the other kobusine derivatives were all inactive. Alkaloid 2, alone, and the 11-acetate (14), 15-acetate (15), 15-propionate (22) and 15-cinnamoate (25) were all active at 1 mg/kg and the effect of 14 at 5 mg/kg was remarkable. The activity of 2 was abolished by esterification of the hydroxyl group at C-6. Alkaloid 15 at 5 mg/kg showed a pattern of time course of blood flow in which the increase was rapidly replaced with a decrease below the basal flow, probably suggesting the effect of excessive doses. Conclusively, it is considered that the hydroxyl groups of alkaloids, especially a free OH group of 2 at C-6, are important for action on the peripheral vasculature leading to dilatation, and these results indicated that esterification of the hydroxyl group at C-15 with either acetate or benzoate may contribute to enhancement of the activity of the parent alkaloids.

Alkaloids↗

Structural characterization of chlorobenzylidine.

AIM: To study the structure and crystal forms of chlorobenzylidine. METHODS: Karl Fischer titrimetry, FTIR, thermal analysis, single and powder X-ray diffraction were used for the studies of the structure of chlorobenzylidine and for the identification of two forms of chlorobenzylidine. RESULTS: Chlorobenzylidine and its diastereoisomer have been studied in this article. They can be distinguished by their different melting points. Two crystal forms of chlorobenzylidine (form A and form B) have also been detected and studied. Form A was studied by single-crystal X-ray diffraction, it crystallized in the triclinic system, space group P1(-), with two formula units per cell, is monohydrate. Karl Fischer titrimetry, FTIR, thermal analysis and powder X-ray diffraction were used for identification of the two forms. CONCLUSION: The studies of structure and crystal forms of chlorobenzylidine are very useful for the clinical research and the selection of recrystallization process.

Benzylidene Compounds↗