Chemical mutagens with an aromatic ring system may be enzymatically transformed to afford aryl radical species that preferentially react at the C8-site of 2'-deoxyguanosine (dG). The resulting carbon-linked C8-aryl-dG adduct possesses altered biophysical and genetic coding properties compared to the precursor nucleoside. Described herein are structural and in vitro mutagenicity studies of a ser...

Pseudouridylation of messenger RNA emerges as an abundant modification involved in gene expression regulation. Pseudouridylation of stop codons in eukaryotic and bacterial cells results in stop-codon read through. The structural mechanism of this phenomenon is not known. Here we present a 3.1-Å crystal structure of Escherichia coli release factor 1 (RF1) bound to the 70S ribosome in response to...

Sickle cell disease affects more than 100,000 individuals in the United States, among whom disease severity varies considerably. One factor that influences disease severity is the sickle cell disease genotype. For this reason, clinical prevention and treatment guidelines tend to differentiate between genotypes. However, previous research suggests caution when using a claimsbased determination o...

The in vivo mutagenicity of 7-hydro-8-oxo-2'-deoxyguanosine (8-oxodG) and N-(guanin-8-yl)-N-acetyl-2-aminofluorene (8-AAFdG) in human cells was determined by transfecting various cell lines with plasmids that carried a single adduct at a defined site. 8-OxodG is one of the many DNA modifications formed by oxygen radicals, and was found to be highly miscoding during replication with purified DNA...

DNA damage and DNA repair may mediate several cellular processes, like replication and transcription, mutagenesis and apoptosis and thus may be important factors in the development and pathology of an organism, including cancer. DNA is constantly damaged by reactive oxygen species (ROS) and reactive nitrogen species (RNS) directly and also by products of lipid peroxidation (LPO), which form exo...

Tactile allodynia can be modeled in experimental animals by acutely blocking spinal glycine or GABA(A) receptors with intrathecal (i.t.) strychnine (STR) or bicuculline (BIC), respectively. To test the hypothesis that glycine and GABA effect cooperative (supra-additive) inhibition of touch-evoked responses in the spinal cord, male Sprague-Dawley rats, fitted with chronic i.t. catheters, were us...

The mutational specificity of the alkylating agent 1-3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) was analyzed at the endogenous hemizygous adenine phosphoribosyl transferase gene of the Chinese hamster ovary cell line D422. A 1-h treatment of the Chinese hamster ovary cells with 50 microM BCNU resulted in a toxicity level of 62% and induced mutation at this target with a frequency of 32.1 mutant...

OBJECTIVES To examine the efficacy of routine examination of multiple causes of death occurring on death certificates in cohort studies, with an example from the oil industry. METHODS The underlying and multiple causes were coded for all notified deaths from a cohort of 35,000 men employed at eight oil refineries in the United Kingdom. Matrices of the frequencies of underlying causes by contr...

Oligonucleotide-directed mutagenesis was used to introduce an A to C transversion at position 523 in the 16S ribosomal RNA gene of Escherichia coli rrnB operon cloned in plasmid pKK3535. E. coli cells transformed with the mutated plasmid were resistant to streptomycin. The mutated ribosomes isolated from these cells were not stimulated by streptomycin to misread the message in a poly(U)-directe...

The toxic, mutagenic, and carcinogenic effects of alkylating agents have been attributed to their ability to damage DNA. Reaction at the O6 position of guanine results in miscoding during DNA replication, has been shown to be mutagenic in both bacteriophage and bacteria, and may be responsible for malignant transformation. In common with many other prokaryotes and eukaryotes the Escherichia col...