Our recent syntheses of chryseno4,5-bcdthiophene together with its potential sulfone metabolite, chryseno4,5-bcdthiophene-4,4-dioxide, have made these compounds available for genotoxicity testing. ...Such toxicity testing is of interest as this thiophene is an isoster of the established carcinogen benzoapyrene and is one of the thiaarenes which are potential environmental contaminants found in fossil fuels. Although the thiophene was less mutagenic than benzoapyrene in Salmonella strains TA98 and TA100 after S9 activation, it exhibited in vivo chromosomal aberration activity equal to that of benzoapyrene in the bone-marrow cells of mice. A reduced activity with Salmonella as well as in the bone-marrow cell assay for the sulfone does not support its role as the key active metabolic intermediate for the genotoxicity of the thiophene. Our molecular orbital calculations would be consistent with the concept of activation through a diol-epoxide mechanism and offers an explanation for the reduced genotoxicity of the sulfone via this mechanism. These genotoxicity studies support the concern that sulfur isosters of established carcinogenic polycyclic aromatic hydrocarbons could themselves be toxic.
We report the observation of the decay $B^{-} \rightarrow D^{(*)+}_{s} K^{-} \ell^{-} \bar{\nu}_{\ell}$ based on $342 \mathrm {\,fb}^{-1}}$ of data collected at the $\Y4S$ resonance with the BABAR ...detector at the PEP-II $e^{+}e^{-}$ storage rings at SLAC. A simultaneous fit to three $D^{+}_{s}$ decay chains is performed to extract the signal yield from measurements of the squared missing mass in the B meson decay. We observe the decay $B^{-} \rightarrow D^{(*)+}_{s} K^{-} \ell^{-} \bar{\nu}_{\ell}$ with a significance greater than five standard deviations (including systematic uncertainties) and measure its branching fraction to be $\BR(B^{-} \rightarrow D^{(*)+}_{s} K^{-} \ell^{-} \bar{\nu}_{\ell}) = 6.13^{+1.04}_{-1.03}(\mathrm{stat.})\pm0.43(\mathrm{syst.}) \pm 0.51(\BR(D_{s}))\times10^{-4}$, where the last error reflects the limited knowledge of the $D_{s}$ branching fractions.
We report a direct measurement of $D^0-overline{D}^0$ mixing parameters through a time-dependent amplitude analysis of the Dalitz plots of $D^0 \rightarrow K_S^0 \pi^+ \pi^-$ and, for the first time, ...$D^0 \rightarrow K_S^0 K^+ K^-$ decays. The low-momentum pion $\pi_s^+$ in the decay $D^{*+} \rightarrow D^0 \pi_s^+$ identifies the flavor of the neutral $D$ meson at its production. Using 468.5 fb$^{-1}$ of $e^+e^-$ colliding-beam data recorded near $\sqrt s = 10.6$~GeV by the BABAR detector at the PEP-II asymmetric-energy collider at SLAC, we measure the mixing parameters $x= 1.6 \pm 2.3 ({\rm stat.}) \pm 1.2 ({\rm syst.}) \pm 0.8 ({\rm model}) \times10^{-3}$, and $y= 5.7 \pm 2.0 ({\rm stat.}) \pm 1.3 ({\rm syst.}) \pm 0.7 ({\rm model}) \times 10^{-3}$. These results disfavor the no-mixing hypothesis with a significance of 1.9 standard deviations, and provide the best measurement to date of $x$.
We report the measurement of the Cabibbo-Kobayashi-Maskawa CP-violating angle $\gamma$ through a Dalitz plot analysis of neutral $D$ meson decays to $K_S^0 \pi^+ \pi^-$ and $K_S^0 K^+ K^-$ produced ...in the processes $B^\mp \to D K^\mp$, $B^\mp \to D^{*} K^\mp$ with $D^* \to D \pi^0,D \gamma$, and $B^\mp \to D K^{*\mp}$ with $K^{*\mp} \to K_S^0 \pi^\mp$, using 468 million $B\bar{B}$ pairs collected by the BABAR detector at the PEP-II asymmetric-energy $e^+e^-$ collider at SLAC. We measure $\gamma=(68 \pm 14 \pm 4 \pm 3)^\circ$ ({\rm mod $180^\circ$}), where the first error is statistical, the second is the experimental systematic uncertainty and the third reflects the uncertainty in the description of the neutral $D$ decay amplitudes. This result is inconsistent with $\gamma = 0$ (no direct CP violation) with a significance of 3.5 standard deviations.
Microbiological risk assessments generally focus on estimating adverse human health risks from exposures to human pathogenic microbes. The assessment of potential human health risks posed by ...pathogens that have acquired resistance to antimicrobial drugs is a new application of risk assessment that is closely related to microbiological risk assessment. Antimicrobial resistance risk assessment is a risk analytical process that focuses on resistance determinants as hazardous agents that might lead to drug-resistant microbial infections in humans exposed to bacteria carrying the determinants. Antimicrobial-resistant infections could occur directly from actively invading or opportunistic pathogens or indirectly from the transfer of resistance genes to other bacteria. Here, we discuss risk assessment models that might be employed to estimate risks from drug-resistant bacteria in the animal food pathway and the types of models and data that may be used for microbiological risk assessments or antimicrobial resistance risk assessments.
The Ames procedure with Salmonella typhimurium strain TA100 was used to follow the detoxication by rat liver fractions of two series of aliphatic epoxides. The epoxides employed were 3-chloro-, ...3,3-dichloro- and 3,3,3-trichloropropylene oxides and also p-methoxyphenyl-, phenyl- and p-nitrophenylglycidyl ethers. In our procedure with preincubation of the epoxides with rat liver fractions prior to the Ames tests, there was more detoxication of both systems by glutathione conjugation (non-enzymatic and transferase promoted) than by the hydrolase pathways. Non-enzymatic reaction with glutathione was more pronounced for the chloro series than for the glycidyl ethers. An HPLC system was developed which was capable of quantitative measurements of the phenylglycidyl ethers together with their diol and glutathione conjugate products. A comparison of the HPLC and Ames test results indicates that the glutathione transferase reported to be present in Salmonella could be playing a role in detoxication by the Ames test. Diols were measured more readily by HPLC than by use of the Ames test in the microsomal fraction and were detected in the cytosol with the glycidyl ethers while they were not by the Ames procedure. However, all three epoxides were converted to a greater extent to their glutathione conjugates than to their diols. Thus, while literature references question the availability of the glutathione detoxication system for epoxides produced by membrane-bound enzymes, such detoxication would be of primary importance where direct-acting environmental epoxides come into contact with the cytosolic enzymes prior to possible reaction with bionucleophiles.
The mutagenicity in Salmonella and in vivo sister chromatid exchange in the bone-marrow cells of mice was determined for 1,4-, 1,3-, 2,4-, and 3,4-dimethylphenanthrene (DMPh) with the objective to ...study the relative importance of substitution at the 1 and 4 positions of this series of methylated phenanthrenes. For both tests, 1,4- DMPh was decidedly more genotoxic than the remaining regioisomers. While the well recognized role of steric crowding in the bay region is a factor in this enhanced genotoxicity, equally important is substitution at the 1 position with its potential to inhibit detoxication through 9,10-diol formation.
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