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We have shown previously that the bleomycin (BLM) carbohydrate moiety can recapitulate the tumor cell targeting effects of the entire BLM molecule, that BLM itself is modular in nature consisting of a DNA-cleaving aglycone which is delivered selectively to the interior of tumor cells by its carbohydrate moiety, and that there are disaccharides structurally related to the BLM disaccharide which are more efficient than the natural disaccharide at tumor cell targeting/uptake. Because BLM sugars can deliver molecular cargoes selectively to tumor cells, and thus potentially form the basis for a novel antitumor strategy, it seemed important to consider additional structural features capable of affecting the efficiency of tumor cell recognition and delivery. These included the effects of sugar polyvalency and net charge (at physiological pH) on tumor cell recognition, internalization, and trafficking. Since these parameters have been shown to affect cell surface recognition, internalization, and distribution in other contexts, this study has sought to define the effects of these structural features on tumor cell recognition by bleomycin and its disaccharide. We demonstrate that both can have a significant effect on tumor cell binding/internalization, and present data which suggests that the metal ions normally bound by bleomycin following clinical administration may significantly contribute to the efficiency of tumor cell uptake, in addition to their characterized function in DNA cleavage. A BLM disaccharide-Cy5** conjugate incorporating the positively charged dipeptide D-Lys-D-Lys was found to associate with both the mitochondria and the nuclear envelope of DU145 cells, suggesting possible cellular targets for BLM disaccharide–cytotoxin conjugates. [ABSTRACT FROM AUTHOR]

Several studies have indicated that mixed brominated/chlorinated organic compounds could be formed during the thermal process such as the incineration of municipal solid waste and open burning of unregulated e-waste at recycling areas. In this study, air particles and soils from e-waste recycling areas, as well as outdoor and indoor air particles from urban Guangzhou, were collected and pooled for the identification of mixed chlorinated/brominated diphenyl ethers (PXDEs). Three monochloro-nonabromo diphenyl ethers (Cl-nonaBDEs), induding 6'-Cl-BDE-206, 5'-Cl-BDE-207, and/or 4'-Cl-BDE-208, were first structurally identified in these air and soil samples. The identification was done by comparison of retention times in chromatograms of pure reference compounds and environmental samples, as well as by comparison with full-scan mass spectra data in electron capture negative ionization mode. Because of their similar physical--chemical properties, 4'-Cl-BDE-208 and 5'-Cl-BDE-207 absolutely coeluted, even on a nonpolar DB-5 column. Further investigation is still needed to clarify these findings. Nevertheless, the results indicated that Cl-nonaBDEs would occur in various environmental matrices. Because the replacement of Br by Cl will change the physical--chemical properties of PBDE analogues, environmental occurrence, fate, and transport, the potential toxicity of PXDEs should be investigated. [ABSTRACT FROM AUTHOR]

Previous studies have reported high serum concentrations of polybrominated diphenyl ethers, especially decabromodiphenyl ether (BDE-209), in the residents of an electronic waste (e-waste) dismantling site in Guiyu town, South China. In the present study, human serum samples in this region were collected and pooled for the identification of hydroxylated diphenyl ethers (OH-PBDEs). Three OH-PBDEs, including two hydroxylated octabromodiphenyl ethers (OH-octaBDEs, 6-OH-BDE196 and 6-OH-BDE199) and one hydroxylated nonabromodiphenyl ether (OH-nonaBDE, 6'-OH-BDE206), were first structurally identified. Identification was done by coeluting a mixture of synthetic authentic standards with the methylated OH-PBDEs from the pooled samples using two gas chromatography columns with different polarities. The results were supported by full scan mass spectrometric data in electron capture negative ionization mode. All three OH-PBDE metabolites had hydroxy groups substituted in the ortho position. These results indicate that hydroxylated higher brominated diphenyl ethers such as OH-octaBDEs and OH-nonaBDEs can accumulate in human blood. The results suggest that higher brominated diphenyl ethers could be oxidatively metabolized into OH-PBDEs in humans. Because low brominated OH-PBDEs can also be detected in abiotic media, further investigations are needed to determine the presence of higher brominated OH-PBDEs in the environment in this region. [ABSTRACT FROM AUTHOR]

Previous studies have reported high serum concentrations of polybrominated diphenyl ethers in residents of an electronic waste (e-waste) dismantling site in Guiyu town, South China. In this study, serum levels of Dechlorane Plus (DP), a chlorinated flame retardant of growing concern, were measured in residents of this region, and compared to those of a matched cohort from a nearby region in Haojiang, where fishing is the dominant industry. DP was detected in all the serum samples, with concentrations ranging from 7.8 to 465 ng/g lipid (median: 42.6 ng/g) and 0.93 to 50.5 ng/g lipid (median: 13.7 ng/g) in Guiyu and Haojiang, respectively. The Pearson's correlation coefficient between DP and decabromodiphenyl ether showed a positive relationship in Guiyu (r = 0.931, p < 0.01), but no correlation in Haojiang (r = 0.321, p = 0.34). The average anti-DP fractional abundances (fanti ratio) were 0.58 ± 0.11 and 0.64 ± 0.05 for Guiyu and Haojiang, respectively (p < 0.01). Tentatively identified dechlorination product ([-Cl + H]) was found in 19/40 serum samples (11/20 for Guiyu, 8/20 for Haojiang). These results suggest that the Guiyu and Haojiang cohorts experienced different dominant exposure routes. It is also possible that DP could bioaccumulate in a stereoselective manner, and undergo dechlorination metabolism. To the best of our knowledge, this is the first study to report DP levels in human serum. Further studies are needed to confirm the results of this study. [ABSTRACT FROM AUTHOR]

Hexabromocyclododecanes (HBCDs) are ubiquitous contaminants in the environment, but little is known on the occurrence and distribution of HBCDs in the background atmosphere of urban environments. In this study, air samples were collected from four sites in the city of Guangzhou, a typical fast developing metropolitan of South China, for quantifying the concentration levels, diasteroisomer profiles, gas-particle distribution and enantiomeric fractions of HBCDs. The results showed that the measured mean atmospheric HBCD concentrations ranged from 0.69 to 3.09 pg/m³, which were similar to those reported from remote or urban sites of the U.S., but were significantly lower than those of Europe. The analysis on diastereoisomer profiles indicated that α-HBCD (59-68%) was the dominant isomer and β-HBCD was a minor isomer in all air samples, which appeared to be different from commercial products. A large variable percentage of HBCDs (69.1-97.3%) are existed in the particle phase, suggesting that long-range tansport of HBCDs might be occur in some environmental conditions. The results of enantiomeric fractions indicated that β and γ-HBCD were racemic mixtures in the tested air samples and that (-)-α-HBCD was slightly enriched in the typical urban site, implying that the HBCDs in these studied sites might be a mixture of emissions from both local sources and soil-air exchange. [ABSTRACT FROM AUTHOR]

Recently, we reported that both bleomycin (BLM) and its disaccharide, conjugated to the cyanine dye Cy5**, bound selectively to cancer cells. Thus, the disaccharide moiety alone recapitulates the tumor cell targeting properties of BLM. Here, we demonstrate that the conjugate of the BLM carbamoylmannose moiety with Cy5** showed tumor cell selective binding and also enhanced cellular uptake in most cancer cell lines. The carbamoyl functionality was required for tumor cell targeting. A dye conjugate prepared from a trivalent cluster of carbamoylmannose exhibited levels of tumor cell binding and internalization significantly greater than those of the simple carbamoylmannose-dye conjugate, consistent with a possible multivalent receptor. [ABSTRACT FROM AUTHOR]