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Biomedical subjects

S A Woski

Publications and source records attributed to S A Woski.

3 recordsLinked to original sources

The nutritional supplement chromium(III) tris(picolinate) cleaves DNA.

Chromium(III) tris(picolinate) [Cr(pic)3] is currently a very popular nutritional supplement; however, its safety has recently been questioned, especially with regard to its ability to act as a clastogen. At physiologically relevant concentrations, Cr(pic)3 is reduced by biological reductants, including ascorbate and thiols, to Cr(II)-containing species. These species are susceptible to air oxidation, resulting in the catalytic generation of the potent DNA-damaging agent hydroxyl radical. In the absence of reductants, H2O2 can interact with Cr(pic)3 to produce hydroxyl radicals by a second, less efficient mechanism. Cr(pic)3 is extremely stable, which allows the complex to be readily absorbed but also to potentially be incorporated into cells intact. In this form, Cr(pic)3 is primed by its redox potential to enter into the generation of hydroxyl radicals. This study suggests that investigation of the long-term effects of supplementation of the diet with Cr(pic)3 are needed to assess the safety of this material.

Animals

An improved route to 1,2-dideoxy-beta-1-phenyl-D-ribofuranose.

An efficient synthesis of the aryl nucleoside analogue 1,2-dideoxy-beta-1-phenyl-D-ribofuranose (1) is described. This route utilizes the addition of phenyllithium to a protected 2-deoxyribonolactone followed by reduction with triethylsilane/boron trifluoride etherate to selectively produce the beta-anomer. Deprotection yields the desired aryl C-nucleoside in 27% overall yield from 2-deoxy-D-ribose.

Deoxyribose

Enhanced high density oligonucleotide array-based sequence analysis using modified nucleoside triphosphates.

Pairs of high density oligonucleotide arrays (DNA chips) consisting of >96 000 oligonucleotides were designed to screen the entire 5.53 kb coding region of the hereditary breast and ovarian cancer BRCA1 gene for all possible sequence changes in the homozygous and heterozygous states. Single-stranded RNA targets were generated by PCR amplification of individual BRCA1 exons using primers containing T3 and T7RNA polymerase promoter tails followed by in vitro transcription and partial fragmentation reactions. Fluorescent hybridization signals from targets containing the four natural bases to >5592 different fully complementary 25mer oligonucleotide probes on the chip varied over two orders of magnitude. To examine the thermodynamic contribution of rU.dA and rA.dT target.probe base pairs to this variability, modified uridine [5-methyluridine and 5-(1-propynyl)-uridine)] and modified adenosine (2,6-diaminopurine riboside) 5'-triphosphates were incorporated into BRCA1 targets. Hybridization specificity was assessed based upon hybridization signals from >33 200 probes containing centrally localized single base pair mismatches relative to target sequence. Targets containing 5-methyluridine displayed promising localized enhancements in hybridization signal, especially in pyrimidine-rich target tracts, while maintaining single nucleotide mismatch hybridization specificities comparable with those of unmodified targets.

Base Pair Mismatch