John T. Shafer

Role of copper transporters in resistance to platinating agents

Copper transporters have been proposed to be involved in cellular import and export of platinating agents. Expression of the human copper transporter 1 (hCtr1) is thought to result in increased sensitivity to cisplatin, whereas expression of ATP7A and ATP7B are thought to be involved in resistance to cisplatin either by sequestering drug away from its targets (ATP7A) or by exporting the drug from the cell (ATP7B). In this study, we evaluated the sensitivity of cells expressing copper transporters to cisplatin, carboplatin and oxaliplatin. We also examined whether O6-benzylguanine, a modulator of platinating agent cytotoxicity, enhanced sensitivity of cells with or without the transporters to cisplatin. Overexpression of hCtr1 in the HEK293 cell line did not result in increased sensitivity to cisplatin, either alone or following treatment with O6-benzylguanine. In contrast, overexpression of ATP7A and ATP7B in Me32a fibroblasts resulted in increased resistance to cisplatin, but not to carboplatin or oxaliplatin. ATP7A-expressing cells (MeMNK) showed a significant enhancement of cisplatin cytotoxicity following O6-benzylguanine treatment, but ATP7B-expressing cells (MeWND) did not. Notably, expression of either ATP7A or ATP7B did not result in a change in total cytoplasmic platinum levels following treatment with BG plus cisplatin. The mechanism of BG enhancement of cisplatin cytotoxicity is not likely through regulation of copper transporters.

A unique glimpse into asteroidal melting processes in the early solar system from the Graves Nunatak 06128/06129 achondrites

Abstract The recently recovered Antarctic achondrites Graves Nunatak 06128 and 06129 are unique meteorites that represent high-temperature asteroidal processes in the early solar system never before identified in any other meteorite. They represent products of early planetesimal melting (4564.25 ± 0.21 Ma) and subsequent metamorphism of an unsampled geochemical reservoir from an asteroid that has characteristics similar to the brachinite parent body. This melting event is unlike those predicted by previous experimental or geochemical studies, and indicates either disequilibrium melting of chondritic material or melting of chondritic material under volatile-rich conditions.

Does Iodate Incorporate into Layered Uranyl Phosphates Under Hydrothermal Conditions

Three new layered uranyl phosphates, Ba(3)(UO(2))(2)(HPO(4))(2)(PO(4))(2), Ba(UO(2))F(PO(4)), and Cs(2)(UO(2))(2)(PO(4))(2), were synthesized under mild hydrothermal conditions. These compounds serve as models for uranium alteration phases that might form when spent nuclear fuel is subjected to oxidizing groundwater containing dissolved phosphate. In order to address the possibility of the incorporation of the key fission product (129)I in the form of iodate into uranyl alteration phases, the substitution of IO(3)(-) for the structurally related PO(3)(OH)(2-) or PO(4)(3-) unit was probed. Iodate incorporation into these phases was investigated using LA-ICP-MS, and these data indicate incorporation of iodine with levels as high as 4162 ppm.

Geochemical fluxes related to alteration of a subaerially exposed seamount: Nintoku seamount, ODP Leg 197, Site 1205

Hole 1205A was drilled on Nintoku Seamount, which lies in the midportion of the Emperor Seamount Chain. This seamount was emergent ∼56 Myr ago but was submerged by 54 Ma, so the lavas have endured weathering in both subaerial and submarine environments. We have studied the petrology, mineralogy, and geochemistry of intercalated altered basalts, breccias, and soil samples recovered at Hole 1205A to quantify the chemical exchanges between the seamount and seawater and/or meteoric fluids. The secondary mineralogy is relatively uniform throughout the section and comprises smectite, Fe-oxyhydroxides, iddingsite, and Ca-carbonates. Soils are composed of variably altered basaltic clasts in a matrix of kaolinite, smectite, and vermiculite with minor goethite, hematite, and magnetite. Throughout the basement section, altered basalts, breccias, and soils are depleted in Si, Mg, Ca, Na, Sr, Rb, and Ba and enriched in Fe. Fe3+/FeT (up to ∼1), δ18O (up to ∼+20‰), and 87Sr/86Sr ratios are strongly elevated relative to primary igneous values. Differences in the 87Sr/86Sr ratios define an Upper Alteration Zone with 87Sr/86Sr close to 56 Ma seawater (∼0.7077) from a Lower Alteration Zone where 87Sr/86Sr are less elevated (∼0.704). The Lower Alteration Zone likely reflects interaction with a subaerial oxidizing fluid at low temperature. This zone probably retained most of the original subaerial weathering signature. The Upper Alteration Zone was altered through circulation of large quantities of cold oxidizing seawater that partially overprinted the subaerial weathering chemical characteristics. Altered samples were compared to estimated protolith compositions to calculate chemical gains and losses. Global chemical fluxes are calculated for the entire basement section using different lithological proportions models and different rates of oceanic island emplacement. Although the global construction rate of ocean islands is small compared to igneous accretion at mid-ocean ridges, the magnitude of the chemical changes indicates that ocean islands and seamounts may be a significant contributor to the chemical budget of the oceans.

Compositional variability in lavas from the Ontong Java Plateau: results from basalt clasts within the volcaniclastic succession at Ocean Drilling Program Site 1184

Abstract Tholeiitic basalts have been recovered from drill sites in different locations on the Ontong Java Plateau (OJP) and are remarkably homogeneous across this large igneous province. The most abundant basalt type is represented by the Kwaimbaita Formation on Malaita in the Solomon Islands, where it is capped by the isotopically distinct and slightly more incompatible-element-enriched basalt of the Singgalo Formation. Ocean Drilling Program (ODP) Leg 192 drilled five sites on the OJP, four of which penetrated basement lava successions. All basalt recovered during Leg 192 is chemically and isotopically indistinguishable from Kwaimbaita-type lavas. Site 1184 of ODP Leg 192 is situated on the eastern salient of the OJP, and is unique because the recovered volcaniclastic succession contains the first conclusive evidence for emergence of part of the OJP above sea level. Within this succession are clasts of basaltic material. We report the major element-, trace-element and isotopic compositions of 14 moderately to highly altered basalt clasts. On the basis of incompatible-element concentrations, specifically high field strength elements (HFSE) and rare earth elements (REE), four groups of clasts are defined. Group 1 clasts are similar to basalt from the Kwaimbaita Formation. Group 2 clasts show variable composition, but the heavy rare earth element (HREE) concentrations are similar to those of basalts from the Kwaimbaita Formation. Group 3 clasts have compositions similar to the high-MgO Kroenke-type basalt recovered during ODP Leg 192. Group 4 clasts are more evolved than the Kwaimbaita or Singgalo lavas, and contain deep negative Eu and Sr anomalies on primitive-mantle (PM)-normalized diagrams, as well as high concentrations of Nb, Ta and Th. Group 4 clasts also show a large fractionation of Nb from La and have (Nb/La)PM ratios of approximately 2. Sr-, Nd- and Pb-isotope ratios were measured on five clasts covering all four groups. Although the Sr- and Pb-isotope ratios exhibit some variability, which we attribute to alteration, the Nd-isotope ratios are within the field defined for Kwaimbaita-type lavas. We conclude that most of the compositional variability displayed by these clasts is a result of alteration and that Ta appears to be the most immobile incompatible trace element. All of the clasts were derived from the mantle source that produced the Kwaimbaita-type and Kroenke-type basalts. Our data emphasize the widespread nature of Kwaimbaita-type basalt and show that the source region was active under both the eastern salient and the high plateau of the OJP.