Effects of 1,4-phenylenebis(methylene)selenocyanate on mutagenesis and p53 protein expression in the tongue of lacI rats treated with 4-nitroquinoline-N-oxide

Previously we showed that the organoselenium compound, 1,4-phenylenebis(methylene)selenocyanate (p-XSC)¹ inhibits 4-nitroquinoline-N-oxide (4-NQO)-induced tongue tumorigenesis in Fisher rats. Here we investigate possible mechanisms of this inhibition by monitoring mutagenesis and p53 protein levels in lacI and conventional Fisher rats treated with: (1) a carcinogenic dose of 4-NQO for 10 weeks in drinking water, (2) 4-NQO + p-XSC (15 ppm as selenium), and (3) 4-NQO followed by p-XSC. For mutagenesis studies, rats were euthanized at 7, 12 or 23 weeks after the start of 4-NQO. For studies on p53 levels, rats were euthanized at 11, 15 and 23 weeks. Appropriate controls were also monitored. In the 4-NQO-alone groups, the mutant fraction (MF) in the cII gene in tongue increased at least 50× background level. The MF (in units of mutants/10⁵ plaque forming units) for the 7, 12, and 23 weeks 4-NQO groups were respectively, 184 ± 88, 237 ± 105, and 329 ± 110. Thus, mutagenesis increased with length of exposure and post-treatment time. p-XSC modestly (ca. 15–30%) inhibited mutagenesis under all conditions. The inhibition reached significance at the last time point. When p-XSC was administered after 4-NQO, the MF was also modestly reduced. In 4-NQO-alone animals, levels of p53 in tongue (determined by Western blotting) were 1, 1.5 and 2.4 control levels at 10, 15 and 23 weeks, respectively. In the p-XSC + 4-NQO group, the enhancement in p53 levels by 4-NQO treatment was decreased about 90% at 15 weeks and 45% (P < 0.05) at 23 weeks, and by slightly smaller percentages in corresponding post-treatment groups. p-XSC alone did not alter p53 levels. As p53 levels generally increase in response to DNA damage, these results suggest that p-XSC reduces 4-NQO-induced DNA damage, resulting in reduced 4-NQO-induced mutagenesis and carcinogenesis. However, the fact that p-XSC is also effective when administered after 4-NQO, suggests additional mechanisms of inhibition exist.     

Characterization of pyrene and chrysene degradation by halophilic Hortaea sp. B15

Bioprocess and Biosystems Engineering - Polycyclic aromatics hydrocarbons (PAHs) are ubiquitous and toxic pollutants that are dangerous to humans and living organism in aquatic environment....     

A critical survey of average distances between catalytic carboxyl groups in glycoside hydrolases

Published X‐ray crystallographic structures for glycoside hydrolases (GHs) from 39 different families are surveyed according to some rigorous selection criteria, and the distances separating 208 pairs of catalytic carboxyl groups (20 α‐retaining, 87 β‐retaining, 38 α‐inverting, and 63 β‐inverting) are analyzed. First, the average of all four inter‐carboxyl O^…O distances for each pair is determined; second, the mean of all the pair‐averages within each GH family is determined; third, means are determined for groups of GH families. No significant differences are found for free structures compared with those complexed with a ligand in the active site of the enzyme, nor for α‐GHs as compared with β‐GHs. The mean and standard deviation (1σ) of the unimodal distribution of average O^…O distances for all families of inverting GHs is 8 ± 2Å, with a very wide range from 5Å (GH82) to nearly 13Å (GH46). The distribution of average O^…O distances for all families of retaining GHs appears to be bimodal: the means and standard deviations of the two groups are 4.8 ± 0.3Å and 6.4 ± 0.6Å. These average values are more representative, and more likely to be meaningful, than the often‐quoted literature values, which are based on a very small sample of structures. The newly‐updated average values proposed here may alter perceptions about what separations between catalytic residues are “normal” or “abnormal” for GHs. Proteins 2014; 82:1747–1755. © 2014 Wiley Periodicals, Inc.     

Direct chromatographic resolution of racemic cyclohexylaminoglutethimide and its acetylated metabolite using cellulose-based chiral stationary phase

Racemic cyclohexylaminoglutethimide (±ChAG) and its acetylated metabolite (±ChAG) were resolved by a direct chromatographic method using a Chiracel OD column without derivatization. Maximum resolutions (R) of 4.89 and 0.74 were obtained for the enantiomers of cyclohexylaminoglutethimide and its acetylated metabolite, respectively.