Vitamin B 12 and the synthesis of thymine and choline in the chick.
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Biomedical subjects
Publications and source records attributed to T R Henderson.
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The influence of diesel fuel composition on mutagenicity of exhaust particle associated organic compounds has been investigated using nine fuels varying in aromatic content and distillation properties. The tests were conducted with Oldsmobile Delta-88 and Peugot 504 diesel cars operated according to the EPA Federal Test Procedure. The particulate exhaust from each test was collected on a filter, extracted in dichloromethane and the resulting extract evaluated for mutagenicity in Salmonella strain TA-100. Mutagenicity of extracts of particles collected from the Oldsmobile were highest in the higher aromatic content fuels (greater than 30%) but similar for intermediate (20%) and low (13%) aromatic content fuels. No influence of aromaticity on mutagenicity was observed in samples collected from the Peugeot under the same conditions. Thus, fuel aromatic content may enhance the production of mutagenic combustion products at higher concentrations, but may be dependent upon engine type. A good correlation was observed between mutagenicity of the particle extracts and the initial boiling point of the fuel (r = 0.89). Gas chromatography/mass spectrometric analysis of the aromatic fraction of the fuels showed that the fuel producing the most mutagenic combustion products was highest in phenanthrene type compounds.
Mutagenic and nonmutagenic extracts of fly ash from fluidized bed combustion were analyzed to determine the compounds responsible for the direct mutagenic activity (mutagenic activity that does not require added metabolic enzymes in the Salmonella mutagenicity assay). Some nitro derivatives of polycyclic aromatic hydrocarbons which are direct acting mutagens were detected by tandem triple quadrupole mass spectrometry. Treatment of a mutagenic and a nonmutagenic extract with excess N2O4 resulted in 28- and 3200-fold increases, respectively, in direct mutagenicity in Salmonella typhimurium strain TA98 and an increase in the relative abundance of nitroaromatic compounds. Polycyclic aromatic compounds were also detected and tentatively identified by gas chromatography-mass spectrometry. Since, previous studies have shown that polycyclic aromatic hydrocarbons may react with NO2 to form direct-acting mutagens, it appears that the direct-acting mutagens in these fly ash extracts may be products of reactions of polycyclic aromatic hydrocarbons with NOX in the combustion gases.
A model system is described in which sustained clonic seizures are produced by a combination of phenytoin (PHT) and pentylenetetrazol (PTZ) in the mouse, the former agent preventing the terminal tonic spasms produced by the latter. In this system, midazolam (MDL), a water-soluble benzodiazepine, was compared with diazepam (DZP), a sparingly soluble agent which is widely used to treat status epilepticus (SE) in humans. Both agents were administered intramuscularly (i.m.) in approximately equieffective doses in animals exhibiting clonic seizure activity. MDL proved to be about twice as potent as DZP. Whereas control animals convulsed for a period of approximately 90 min, those treated with DZP 0.2 and 0.4 mg/kg convulsed for 7.8 and 3.9 min, respectively; mice receiving MDL 0.1 and 0.2 mg/kg convulsed for 1.9 and 1.4 min, respectively. MDL arrested seizures substantially more rapidly than diazepam (p less than 0.05). These data suggest that MDL has sufficiently rapid anticonvulsant action to merit evaluation for control of SE in humans when a rapidly absorbed antiepileptic drug (AED) is needed and intravenous (i.v.) administration is not feasible.