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J C Phillips

Publications and source records attributed to J C Phillips.

At least 109 records · Page 6Linked to original sources
PubMed1972

Disequilibrium in the malate dehydrogenase reaction in rat liver mitochondria in vivo.

1. When [2-(14)C]pyruvate is injected into rats the C3-position of liver glutamate becomes more heavily labelled than the C2-position, thus establishing that oxaloacetate and fumarate are not in equilibrium in rat liver mitochondria in vivo. The amount of disequilibrium was shown to be simply related to the value that the C3-label/C2-label ratio would have were no label recycled. This ratio, z, was calculated for post-absorptive rats in environmental temperatures of 20 degrees and 30 degrees C from determinations of the distribution of label within glutamate 1, 3 and 10min after intravenous injection of [2-(14)C]pyruvate. The values of z (best estimate and range) were 1.65 (1.60-1.69) in rats at 20 degrees C and 2.43 (2.23-2.63) in rats at 30 degrees C. These values of z imply the following rates of interconversion in mitochondria of fumarate and oxaloacetate (in terms of the oxaloacetate-->citrate flux, R) in rats at 20 degrees C: [Formula: see text] and in rats at 30 degrees C: [Formula: see text] 2. The kinetic parameters of malate dehydrogenase and fumarate hydratase and the intramitochondrial concentrations of NAD(+) and NADH under (as far as could be judged) conditions in vivo were collated. From them and the best estimates of R now available were calculated the rates of interconversion of fumarate, malate and oxaloacetate required to give the found values of z. These rates showed that the fumarate hydratase reaction was nearly in equilibrium, but that the malate dehydrogenase reaction was considerably out of equilibrium. The calculations also led to the following conclusions. 3. In livers of rats at 20 degrees and 30 degrees C mitochondrial malate concentrations were respectively about 5 and 1.5 times mean cellular concentrations. 4. Mitochondrial oxaloacetate concentrations were less than 0.2 of the mean cellular concentrations. They were also only 0.65 and 0.55 of the equilibrium concentrations for the malate dehydrogenase reaction in rats at 20 degrees and 30 degrees C respectively. 5. Malate dehydrogenase activity was low because of the very low oxaloacetate concentrations in the mitochondria and the very small fraction of the enzyme complexed with NAD(+), i.e. in each direction one substrate concentration was very sub-optimal.

Animals↗
PubMed1972

Simple liquid scrubber for large-volume air sampling.

A new large-volume air sampler called the "simple liquid scrubber" is described. It can recover a high percentage of microorganisms from large volumes of air, up to 950 liters/min, and concentrate them into a small volume of liquid at a ratio of about 400,000 to 1. The principle of operation of the scrubber is based on the production of a fine mist in a rapidly moving airstream with ultimate collection of the airborne particles by impingement into the film of liquid formed upon impaction of the mist droplets on the scrubber walls. The scrubber compared favorably with the all-glass impinger (AGI-30) and the slit sampler in tests with the normal flora and with experimental aerosols of Bacillus subtilis var. niger spores.

Acrylic Resins↗
PubMedDate not supplied

DNA adducts produced by oils, oil fractions and polycyclic aromatic hydrocarbons in relation to repair processes and skin carcinogenesis.

Ten polycyclic aromatic hydrocarbons (PAHs) mainly with three or four aromatic rings were tested for their ability to induce DNA adduct formation in mouse skin. Four of these were selected to investigate adduct formation and loss over a period of 8 days. Three mineral oils were also examined for their adduct forming ability and one was selected for adduct formation and loss over a period of 8 days. In addition, fractions derived from the same oil containing 2-3- and 4-6-ring aromatic compounds were applied to mouse skin in a non-carcinogenic oil vehicle and adduct levels were observed over an 8-day period. It was found that PAHs that had no mutagenic, initiating or carcinogenic activity and those that had mutagenic activity in bacteria but no initiating activity in mouse skin failed to produce DNA adducts in mouse skin. Two of the three PAHs with initiating activity and both complete carcinogens produced clear evidence of adduct formation, the adduct levels produced by complete carcinogens being 100-1000 times greater than those produced by initiators. Examination of adduct formation and loss with the carcinogenic PAHs benzo[a]pyrene and 5-methylchrysene over an 8-day period showed a peak at 24 h and an apparent two-phase process of adduct loss. It is suggested that the first steep loss was due to DNA repair and that the more gradual subsequent loss was probably due to epidermal hyperplasia and desquamation. With the initiator 1, 4-dimethylphenanthrene (three rings) a peak of adduct formation was seen at 2 days and adduct levels were not reduced much by 8 days. This suggested that, with initiators, adduct formation and repair may be spread over a longer period than with complete carcinogens. With the whole oils, clear evidence of adduct formation was seen with both a carcinogenic non-solvent-refined oil and with a non-carcinogenic residual oil. The level of adduct formation with the residual oil, however, was much lower than with the carcinogenic oil. When adduct formation by the carcinogenic oil was examined over 8 days, the pattern of adduct formation and loss was similar to that of a tumour initiator rather than a complete carcinogen. Peak adduct levels on the diagonal of the thin-layer chromatography (TLC) plates seemed to occur at 1 and 4 days after treatment, with no clear reduction after 8 days. From examination of adducts formed by the 2-3-ring and 4-6-ring aromatic fractions, it appeared that the main adduct spots produced by the carcinogenic oil were due to the 2-3-ring aromatic components of the oil. Adduct spots near the vertical axis of the TLC plates were also seen with the 2-3-ring and 4-6-ring fractions. The relevance of these spots is uncertain, but if they truly represent adducts, the findings suggest that they are due mainly to 4-ring PAHs. The studies suggest that the activity of carcinogenic oils is largely due to substituted 3- and 4-ring polycyclic aromatic compounds and that more attention should be paid to substituted 3-ring compounds in predicting the carcinogenic potential of oils from analytical data.

Animals↗
PubMedDate not supplied

The dermal bioavailability of radiolabelled benzo[a]pyrene from acetone or from oils of differing viscosity, assessed by DNA and protein binding.

Tritium-labelled benzo[a]pyrene ([3H]BaP) was applied to mouse skin in acetone or mineral oils of differing viscosity. Epidermal DNA and protein were extracted after 24 or 48 h and the degree of adduct formation determined by the radioactivity present. When [3H]BaP was applied in acetone, the degree of DNA and protein binding was around 15-20 times greater than that observed when a low-viscosity oil was used as a vehicle. When applied in oils of differing viscosity, however, only a twofold difference was seen across the whole viscosity range (13.5 cSt* at 40 degrees C to 1665 cSt at 60 degrees C). From measurements made of urine and faecal radioactivity and from small-scale investigations using other routes of administration, it was clear that the grooming activity of the animals had a marked effect on skin absorption and macromolecular binding. It is possible that greater grooming activity with low-viscosity oils may explain why oil viscosity did not have a greater effect on binding levels, but further studies are needed to investigate this. These findings may have important implications in the interpretation of long-term skin painting studies and may assist in the interpretation of analytical data and short-term biological assays.

Acetone↗
PubMedDate not supplied

Factors affecting the bioavailability of benzo[a]pyrene from oils in mouse skin: oil viscosity, grooming, activity and its prevention.

In the main study, tritium-labelled benzo[a]pyrene ([3H]BaP) was added to oils of a wide range of viscosity (from 13.5 to ca. 8000 cSt at 40 degrees C) and these were applied once to mouse skin under conditions where grooming was either allowed or prevented. The binding of [3H]BaP to epidermal protein and DNA was assessed. In addition, some studies were conducted to investigate the effect of prior oil exposure on binding levels and to compare binding levels following single and multiple application. It was found in the main study that the binding of [3H]BaP to both DNA and protein was increased as the viscosity of the oil vehicle decreased. Whereas only a twofold difference in DNA binding was found between the lowest and highest viscosity oil vehicle if grooming was allowed, a 14-fold difference was seen if grooming was prevented. This was due to much higher binding levels with low viscosity oils when grooming was prevented. Protein binding showed similar results, although the difference between the grooming and non-grooming situations was slightly less. Whether grooming was prevented or not, both DNA and protein binding of [3H]BaP were found to be inversely proportional to the logarithm of viscosity of the oil vehicle, but when grooming was prevented, the slope for DNA binding was 10 times steeper than when it was permitted. Exposure of the skin to either high or low viscosity oils prior to the application of [3H]BaP in the same oil inhibited the binding to DNA but not to protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

DNA adduct formation by mineral oils and their fractions as indicated by 32P-postlabelling: is adduct formation truly indicative of carcinogenic potential?

Oils of differing types, physical properties and carcinogenic activity were tested for ability to produce epidermal DNA adducts 24 h after application to the skin of mice, using the 32P-postlabelling method. Two studies were carried out, the first on three oils to identify the adduct-forming components, and the second on nine oils to investigate whether the nature of the oils affected their adduct-forming potential. In addition to the whole oils, fractions of the oils containing saturated hydrocarbons, 2-6-ring aromatic compounds and polar compounds were tested in both studies in proportion to their concentration in the original oil. In addition, a further examination of the aromatic fractions from two carcinogenic oils was carried out in the first study by testing 2-3-ring and 4-6-ring subfractions (the latter containing carcinogenic polycyclic aromatic compounds (PACs)). Results from the first study indicated that carcinogenic oils do produce adducts and that the adduct-forming components were mainly in the aromatic fraction. When, however, subfractions of the aromatic fraction were examined, it was found that slightly higher adduct levels were produced by the 2-3-ring aromatic fraction than with the 4-6-ring PAC fraction. This was contrary to expectation from published work on the skin carcinogenicity of oils and suggested that some non-carcinogenic PACs may produce adducts. The second study indicated that although most carcinogenic oils produced adducts, some non-carcinogenic oils can also do so.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Comparative metabolism of BHA, BHT and other phenolic antioxidants and its toxicological relevance.

Following oral administration, butylated hydroxyanisole (BHA) is absorbed and rapidly excreted by the rat, rabbit and man, with little evidence of long-term tissue storage. The major metabolic pathways for BHA are conjugation (phase 2) reactions, oxidative metabolism (O-demethylation) being relatively unimportant. In the dog, the extent of absorption and urinary excretion is less, and oxidative metabolism is more important than in other species. In contrast, butylated hydroxytoluene (BHT) is cleared less rapidly from most species, enterohepatic circulation being partly responsible for the delay. Tissue accumulation is also greater for BHT than for BHA. Oxidative metabolism (phase 1 reactions) mediated by the microsomal monooxygenase system is the major route for BHT degradation; oxidation of the ring methyl group predominates in the rat, rabbit and monkey, and oxidation of the tert-butyl groups in man. Gallates and 2-tert-butylhydroquinone are mainly metabolized by non-oxidative pathways (methylation or conjugation with sulphate and glucuronic acid). The different biological properties of these compounds may be related to the differences in their absorption and metabolic disposition. Thus, whereas BHT, which is metabolized by oxidation reactions, is an inducer of the microsomal mono-oxygenase system, the other phenolic antioxidants, including BHA, are only weak inducers.

Animals↗
PubMedDate not supplied

An evaluation of the decision tree approach for assessing priorities for safety testing of food additives.

In this publication we report an evaluation of the decision tree scheme of Cramer, Ford and Hall (1978) for assigning priorities for toxicity testing of chemicals. The original scheme has been modified to allow more chemical structures to be considered and to take into account recent advances in toxicology. The majority of the food additives permitted in either the UK, USA or Canada have been processed through the modified decision tree questionnaire and their classification compared with currently available chronic toxicity data. A large proportion of the additives (53/73) assigned to the lowest toxicity (I) class have a low order of chronic oral toxicity as do many of the compounds assigned to the moderate toxicity (II) class. Although the majority of the additives assigned to the highest toxicity (III) class are substantially more toxic than those in the lower toxicity classes, some relatively innocuous compounds reached this classification. In addition, a few toxic compounds were assigned to the lowest toxicity class. The reasons for these incorrect assignments are discussed. It was concluded that the decision tree approach, although less discriminating than originally suggested, remains a useful method for classifying compounds in terms of their probable toxicity and that further modifications to the tree could be made.

Accident Prevention↗
PubMedDate not supplied

Measurement of trazodone using solid-phase extraction and wide-bore capillary gas chromatography with nitrogen-selective detection.

A method for the determination of the antidepressant drug trazodone is presented. 8-Hydroxyloxapine is used as the internal standard. A simple solid-phase extraction procedure utilizing disposable reversed-phase C18 columns is described. Samples are analyzed by gas chromatography with nitrogen-selective detection using a wide-bore capillary column with a permanently bonded, nonpolar stationary phase. The assay possesses linearity to 3.0 micrograms/mL, sensitivity to at least 0.25 microgram/mL, recovery averaging 96%, and between-run precision reflected by a CV of 5.6%. We conclude that the method reported here is ideally suited for monitoring therapeutic and toxic levels of trazodone.

Chromatography, Gas↗