Ethenoguanines undergo glycosylation by nucleoside 2'-deoxyribosyltransferases at non-natural sites.

Deoxyribosyl transferases and functionally related purine nucleoside phosphorylases are used extensively for synthesis of non-natural deoxynucleosides as pharmaceuticals or standards for characterizing and quantitating DNA adducts. Hence exploring the conformational tolerance of the active sites of these enzymes is of considerable practical interest. We have determined the crystal structure at 2.

Quantitative monitoring of dermal and inhalation exposure to 1,6-hexamethylene diisocyanate monomer and oligomers.

Respiratory sensitization and occupational asthma are associated with exposure to 1,6-hexamethylene diisocyanate (HDI) in both monomeric and oligomeric forms. The monomer and polymers of diisocyanates differ significantly in their rates of absorption into tissue and their toxicity, and hence may differ in their contribution to sensitization. We have developed and evaluated a liquid chromatography/mass spectrometry (LC-MS) method capable of quantifying HDI and its oligomers (uretidone, biuret, and isocyanurate) in air, tape-stripped skin, and paint samples collected in the automotive refinishing industry.

Quantitative analysis of N-terminal valine peptide adducts specific for 1,2-epoxy-3-butene.

Butadiene (BD) metabolism shows gender, species and concentration dependency, making the extrapolation of animal results to humans complex. BD is metabolized mainly by cytochrome P450 2E1 to three epoxides, 1,2-epoxy-3-butene (EB), 1,2;3,4-diepoxybutane (DEB) and 1,2-epoxy-butanediol (EB-diol). For accurate risk assessment it is important to elucidate species differences in the internal formation of the individual epoxides in order to assign the relative risks associated with their different mutagenic potencies.

Tape-strip sampling for measuring dermal exposure to 1,6-hexamethylene diisocyanate.

Objectives: This study describes the development and evaluation of a method for sampling layers of the stratum corneum for the quantitation of dermal exposure to 1,6-hexamethylene diisocyanate (HDI).

Methods: HDI deposited on skin was collected by the removal of stratum corneum with adhesive tape, derivatized with 1-(2-methoxyphenyl)piperazine, and quantitated as the urea derivative (HDIU) by liquid chromatography-mass spectrometry (LC-MS). This LC-MS method was tested by analyzing tape spiked with HDI-containing products, then applied to tape samples collected from the skin of an auto-body shop worker exposed to polyurethane paint aerosols.

Analysis of diepoxide-specific cyclic N-terminal globin adducts in mice and rats after inhalation exposure to 1,3-butadiene.

1,3-Butadiene is an important industrial chemical used in the production of synthetic rubber and is also found in gasoline and combustion products. It is a multispecies, multisite carcinogen in rodents, with mice being the most sensitive species. 1,3-Butadiene is metabolized to several epoxides that form DNA and protein adducts.

1,N2-propanodeoxyguanosine adducts of the 1,3-butadiene metabolite, hydroxymethylvinyl ketone.

1,3-Butadiene (BD) is a rodent and human carcinogen. While several epoxides formed during BD metabolism are mutagenic and may contribute to BD carcinogenicity, another proposed metabolite, hydroxymethylvinyl ketone (HMVK), could also be involved. A significant quantity of HMVK is likely to be formed since it is a proposed intermediate in the metabolism of 3-butene-1,2-diol (BD-diol) to 1,2-dihydroxy-4-(N-acetylcysteinyl)butane, the major mercapturic acid metabolite of BD in humans.