Induction of aberrant mitosis with PCBs: particular efficiency of 2, 3,3',4,4'-pentachlorobiphenyl and synergism with triphenyltin. (1/122)

The polychlorinated biphenyls 2,2',5,5'- and 3,3',4, 4'-tetrachlorobiphenyl, 2,3,3',4,4'- and 3,3',4,4', 5-pentachlorobiphenyl and 2,2',4,4',5,5'-hexachlorobiphenyl were tested for spindle-disturbing activity in V79 Chinese hamster cells. Clones lacking endogenous cytochrome P450 activity or expressing rat CYP1A1 or CYP2B1 were used. Induction of abnormal chromosomal arrangements in mitosis were found to be favoured by o-chlorine substitutions, but not by co-planarity giving affinity, for example, for the Ah receptor and CYP1A isoenzymes. Only 2,2',5, 5'-tetrachloro- and 2,3,3',4,4'-pentachlorobiphenyl gave dose-response curves similar to many other compounds tested in vitro, showing an increase from the background level of 10 to 100% disturbed mitoses with nominal concentrations >10(-6) M, i.e. concentrations far above the total PCB concentrations found in human blood. Cells transfected with rat CYP2B1 were more sensitive to the most active congener, 2,3,3',4,4'-pentachlorobiphenyl, than cells lacking P450 activity or expressing CYP1A1. Induction of abnormal mitosis by PCB metabolites formed by P450 enzymes cannot be excluded, but does not seem likely because of the short treatment time and the reportedly slow metabolism of PCBs. 2,3,3',4, 4'-Pentachlorobiphenyl showed synergistic activity with the potent spindle poison triphenyltin. Inactive concentrations of both agents (10 and 50 nM, respectively) caused abnormal configurations when combined. This is an important finding since exposure to mixtures of compounds is common and it motivates further studies of subthreshold activities of highly lipophilic environmental contaminants.  (+info)

Studies on transfer ribonucleic acids and related compounds. IX. Ribooligonucleotide synthesis using a photosensitive o-nitrobenzyl protection at the 2'-hydroxyl group. (2/122)

o-Nitrobenzyl group was introduced to the 2'-hydroxyl function of uridine via 2',3'-O-(dibutylstannylene) uridine. The benzylated uridine was protected at the 5'-hydroxyl group with monomethoxytrityl chloride and condensed with 2',3'-O-dibenzoyluridine 5'-phosphate or N,N',2',3'-O-tetrabenzoyladenosine 5'-phosphate using dicyclohexylcarbodiimide (DCC). o-Nitrobenzyl ether linkage of the dinucleotides was removed by UV irradiation with wavelength longer than 320 nm. Deprotected UpU and UpA thus obtained were characterized by RNase A digestion.  (+info)

Degradation of triphenyltin by a fluorescent pseudomonad. (3/122)

Triphenyltin (TPT)-degrading bacteria were screened by a simple technique using a post-column high-performance liquid chromatography using 3,3',4',7-tetrahydroxyflavone as a post-column reagent for determination of TPT and its metabolite, diphenyltin (DPT). An isolated strain, strain CNR15, was identified as Pseudomonas chlororaphis on the basis of its morphological and biochemical features. The incubation of strain CNR15 in a medium containing glycerol, succinate, and 130 microM TPT resulted in the rapid degradation of TPT and the accumulation of approximately 40 microM DPT as the only metabolite after 48 h. The culture supernatants of strain CNR15, grown with or without TPT, exhibited a TPT degradation activity, whereas the resting cells were not capable of degrading TPT. TPT was stoichiometrically degraded to DPT by the solid-phase extract of the culture supernatant, and benzene was detected as another degradation product. We found that the TPT degradation was catalyzed by low-molecular-mass substances (approximately 1,000 Da) in the extract, termed the TPT-degrading factor. The other fluorescent pseudomonads, P. chlororaphis ATCC 9446, Pseudomonas fluorescens ATCC 13525, and Pseudomonas aeruginosa ATCC 15692, also showed TPT degradation activity similar to strain CNR15 in the solid-phase extracts of their culture supernatants. These results suggest that the extracellular low-molecular-mass substance that is universally produced by the fluorescent pseudomonad could function as a potent catalyst to cometabolite TPT in the environment.  (+info)

A photobiological and photophysical-based study of phototoxicity of two chlorins. (4/122)

To understand the fundamental determinants of phototoxic efficacy and absorbed photodynamic dose, the triplet state and photobleaching quantum yields in living cells, cellular uptake, intracellular localization, and correlation with cell viability were studied for the two purpurins tin ethyl etiopurpurin 1 (SnET2) and tin octaethylbenzochlorin (SnOEBC) in ovarian cancer cells (OVCAR5). Although the triplet yields of these two photosensitizers were not significantly affected by cellular incorporation, the photobleaching yields were shown to be 3 orders of magnitude higher for cellular-bound sensitizer than for free or albumin-bound photosensitizer and higher for SnET2 than for SnOEBC for all of the cases. The intracellular concentration of SnOEBC was half that of SnET2 after 3 h- and 24 h-incubation times for both 0.1 microM and 1.0 microM incubation concentrations. Despite the lower concentrations of SnOEBC, the phototoxicity of the two photosensitizers was comparable at 1-microM incubation concentration and was up to 10-fold higher for SnOEBC at the lower concentration. The subcellular localization established using confocal microscopy and molecular probes showed that both photosensitizers were primarily lysosomally localized. SnOEBC, however, had an extra-lysosomal, mitochondrial localization component. The photophysical measurements allowed calculation of the intracellular singlet oxygen production, which indicated that the photosensitizer-light dose reciprocity was limited by photobleaching for SnET2 but only minimally for SnOEBC, and this was confirmed through cell-survival studies. Taken together, these data indicate that the critical determinant of differences in phototoxicity between the two molecules was their relative rates of photobleaching and their subcellular localization. The study points to the importance of combining photosensitizer uptake and localization with photophysical measurements in the relevant biological milieu to reasonably interpret and/or predict photosensitization efficacies.  (+info)

Interaction of diphenyltin(IV) dichloride with some selected bioligands. (5/122)

The interaction of diphenyltin(IV) with selected bioligands having a variety of model functional groups were investigated using the potentiometric technique. The hydrolysis constants of diphenyltin(IV) cation and the step-wise formation constants of the complexes formed in solution were calculated using the non linear least-squares program MINIQUAD-75. The participation of different ligand functional groups in binding to organotin is discussed. The concentration distribution of the various complex species was evaluated as a function of pH.  (+info)

Organotin compounds alter the physical organization of phosphatidylcholine membranes. (6/122)

Organotin compounds have a broad range of biological activities and are ubiquitous contaminants in the environment. Their toxicity mainly lies in their action on the membrane. In this contribution we study the interaction of tributyltin and triphenyltin with model membranes composed of phosphatidylcholines of different acyl chain lengths using differential scanning calorimetry, (31)P-nuclear magnetic resonance, X-ray diffraction and infrared spectroscopy. Organotin compounds broaden the main gel to liquid-crystalline phase transition, shift the transition temperature to lower values and induce the appearance of a new peak below the main transition peak. These effects are more pronounced in the case of tributyltin and are quantitatively larger as the phosphatidylcholine acyl chain length decreases. Both tributyltin and triphenyltin increase the enthalpy change of the transition in all the phosphatidylcholine systems studied except in dilauroylphosphatidylcholine. Organotin compounds do not affect the macroscopic bilayer organization of the phospholipid but do affect the degree of hydration of its carbonyl moiety. The above evidence supports the idea that organotin compounds are located in the upper part of the phospholipid palisade near the lipid/water interface.  (+info)

Organotin compounds promote the formation of non-lamellar phases in phosphatidylethanolamine membranes. (7/122)

Organotin compounds are important contaminants in the environment. They are membrane active molecules with broad biological toxicity. We have studied the interaction of tri-n-butyltin chloride and tri-n-phenyltin chloride with model membranes composed of different phosphatidylethanolamines using differential scanning calorimetry, X-ray diffraction, 31P-nuclear magnetic resonance and infrared spectroscopy. Organotin compounds laterally segregate in phosphatidylethanolamine membranes without affecting the shape and position of the lamellar gel to lamellar liquid-crystalline phase transition thermogram of the phospholipid. This is in contrast with their reported effect on phosphatidylcholine membranes [Chicano et al. (2001) Biochim. Biophys. Acta 1510, 330-341] and emphasises the importance of the nature of the lipid headgroup in determining how the behaviour of lipid molecules is affected by these toxicants. Interestingly, we have found that organotin compounds disrupt the pattern of hydrogen-bonding in the interfacial region of dielaidoylphosphatidylethanolamine membranes and have the ability to promote the formation of hexagonal H(II) structures in this system. These results open the possibility that some of the specific toxic effects of organotin compounds might be exerted through the alteration of membrane function produced by their interaction with the lipidic component of the membrane.  (+info)

Comprehensive-trace level determination of methyltin compounds in aqueous samples by cryogenic purge-and-trap gas chromatography with flame photometric detection. (8/122)

A comprehensive method was developed for the sensitive and fast determination of trace levels of methyltin compounds in aqueous samples. Tin compounds in aqueous solution at pH 5 were converted to the corresponding volatile hydrides: CH3SnH3, (CH3)2SnH2, and (CH3)3SnH, by reaction with potassium borohydride. A CP-4010 purge and trap injector (PTI) was used to purge analyte species from water directly. The volatile derivatives were base-line separated on a capillary column in an Angilent-6890 gas chromatograph by a suitable temperature program and were detected by a flame photometric detector (FPD). The detection limits were 18 ng L-1 for monomethyltin, 12 ng L-1 for dimethyltin, and 3 ng L-1 for trimethyltin, respectively. This method was successfully applied to the determination of methyltin compounds in different aqueous samples.  (+info)

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