Pharmacokinetic and organ distribution studies of liposomal drugs in humans are a challenge. A direct labeling method using 99m

This paper describes a simple and inexpensive procedure to produce thin-films of poly(dimethylsiloxane). Such films were characterized by a variety of techniques (ellipsometry, nuclear magnetic resonance, atomic force microscopy, and goniometry) and used to investigate the adsorption kinetics of three model proteins (fibrinogen, collagen type-I, and bovine serum albumin) under different conditions. The information collected from the protein adsorption studies was then used to investigate the adhesion of human dermal microvascular endothelial cells. The results of these studies suggest that these films can be used to model the surface properties of microdevices fabricated with commercial PDMS. Moreover, the paper provides guidelines to efficiently attach cells in BioMEMS devices.

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Alkylation of DNA by 7r,8t-dihydroxy,9t,10t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) forms mainly trans adducts (with respect to the C-9͞10 positions). We recently described a halide-catalyzed pathway that preferentially generates cis adducts and now report that the trans chlorohydrin of anti-BPDE (trans-BPDCH) is an intermediate in the chloride-catalyzed reaction. trans-BPDCH was synthesized, and both it and anti-BPDE were reacted with deoxyadenosine as a model DNA nucleophile. The stereochemistry and yields of deoxyadenosine adducts were determined as a function of chloride concentration. In the absence of salt, the fraction of cis adducts obtained from anti-BPDE and trans-BPDCH are 0.33 and 0.67, respectively. Adding sodium chloride increases the fraction of cis adducts (and consequently decreases the fraction of trans adducts), with the midpoint of the increase for both substrates at approximately 35-40 mM chloride. The chloride-dependent curves for BPDE and BP-DCH converge at 1 M chloride, where the fraction of cis adducts is 0.88. Chloride also increases the total yield of cis adducts with either substrate, whereas the yield of trans adducts from the chlorohydrin is not significantly changed. These results support a mechanism by which chloride ion undergoes nucleophilic addition to the benzylic C-10 position of anti-BPDE. This generates a trans halohydrin that alkylates DNA with inversion of configuration to form a cis adduct. This pathway may have biological significance because chlorohydrins could form in serum or in cells with relatively high intracellular concentrations of chloride.Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants, and a number of these hydrocarbons, including benzo[a]pyrene, are potent carcinogens. Benzo [a]pyrene is cytotoxic and mutagenic, and induces cell transformation in culture (1, 2). Although benzo [a]pyrene is a weak complete carcinogen, it is an initiator and interacts strongly with DNA, causing mutations and chromosomal damage (2).Benzo [a]pyrene is metabolically activated by a series of reactions to form several isomeric bay region diol epoxides (3). The most mutagenic and carcinogenic of these is (7R,8S)-dihydroxy-(9S,10R)-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(ϩ)-anti-BPDE]; this isomer is also the one formed in highest amounts in vivo (3-5). BPDE and other activated PAH carcinogens probably initiate tumors by alkylation of DNA. The primary alkylation site of (ϩ)-anti-BPDE is the exocyclic amino group of deoxyguanosine (3, 6-10). Minor adducts are formed by alkylation of the exocyclic amino group of deoxyadenosine (dAdo) and, to a lesser extent, that of deoxycytidine (9,11,12). In addition, BPDE forms an unstable adduct at the N-7 position of deoxyguanosine, which results in depurination (13). Another pathway of PAH activation is by metabolic conversion to radical cations (14), which alkylate DNA to form adducts that are also lost by depurination.The formation of adducts between bay region diol epoxides and DNA has be...

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