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Biomedical subjects

B R Clark

Publications and source records attributed to B R Clark.

At least 73 records · Page 4Linked to original sources
PubMed1979

Skin carcinogenicity of synthetic and natural petroleums.

In a series of three separate experiments mice were exposed to various concentrations of fossil liquids obtained from coal, oil shale or natural petroleum. All materials were capable of inducing squamous cell carcinoma, but potency differed substantially. Skin carcinogenicity was markedly greater for both coal or oil shale liquids than for natural petroleums. None of the syncrudes approached the skin carcinogenicity of a pure reference carcinogen, benzo(a)pyrene (BP). It is unlikely that determination of the concentration of an active compound in material applied to the test animal will allow meaningful comparison among the diverse agents of interest to the synthetic fuels industry. To better establish the relationship between actual tissue dose and surface concentration the authors are investigating various in vitro and biochemical measures of hydrocarbon-skin interaction to determine which, if any, could serve as a more definitive measure of surface dose. Results, using BP as a marker carcinogenic hydocarbon, suggest that carcinogenic crudes inhibit both BP metabolism in skin organ culture and the interaction of BP adducts with epidermal DNA, in vivo.

Animals↗
PubMed1978

Analytical and biological analyses of test materials from the synthetic fuel technologies. I. Mutagenicity of crude oils determined by the Salmonella typhimurium/microsomal activation system.

We have assayed the mutagenicity of crude industrial products and effluents with the Salmonella/microsomal activation system. Test materials (crude products from coal-conversion processes and natural crude oils) were initially fractionated into primary classes by liquid--liquid extraction and then further fractionated by column chromatography. Prescreening was accomplished over a wide concentration range with the Ames tester strains. Active fractions (mainly the neutral fractions containing polycyclic aromatic hydrocarbons and certain basic fractions) can be identified, and dose--response relationships can be established. Standard values are expressed as revertants/mg of the test material assayed with frameshift strain TA98 including metabolic activation with rat-liver preparations. Total mutagenic activity of synthetic fuel samples was consistently higher than that of natural crude "controls." Activities of subfractions are roughly additive and presumably reflect the mutagenic potential of the whole test material. These results are being extended to other genetic assays. Chemical identification is carried out along with the bioassays.

Coal↗
PubMed1977

Pyrimidine metabolism during restorative brain growth after neonatal undernutrition in the rat.

Three litters of 20 Wistar rat pups each were maintained until age 6 days at which time only the 4 lightest and 4 heaviest pups from each litter were left with the mother until age 13 days. Three control litters of eight pups each were also maintained for 13 days. At that time, the undernourished light pups showed body weight, cerebellar weight, and cerebellar DNA, respectively, of 79.2%, 86.6%, and 90.4% compared with a "combined control" group consisting of control pups plus undernourished heavy pups which were statistically indistinguishable with regard to these three measurements. After the week of "catch-up" or restorative body and brain growth, activities of enzymes from metabolic pathways leading to pyrimidine and nucleic acid biosynthesis were measured in cerebella from all three groups (control, undernourished heavy, and undernourished light). The salvage pathway enzyme thymidine kinase (TK) and the inter-conversion pathway enzyme thymidylate synthetase (TS) in the undernourished light group showed significant elevations of 32% and 11%, respectively, above activity in the combined control group. The salvage pathway enzyme uridine kinase (UK) and the de novo pathway enzyme aspartate transcarbamylase were not significantly different in cerebella from these two groups. The significant elevation in TK and TS in undernourished pups suggest that these enzymes are critical for restorative brain growth. The significant elevation of TS indicates that the inter-conversion pathway converting available uridylate, a ribonucleotide, to thymidylate, a deoxyribonucleotide, is activated in order to augment DNA biosynthesis.

Age Factors↗
PubMed1975

New approach to antifolate treatment of certain cancers as demonstrated in tissue culture.

The selective toxicity of antifolates for a variety of cancers can be improved, as illustrated by the combined administration of N5-methyltetrahydrofolate and methotrexate in tissue culture. When a variety of neoplastic cell types characterized by a deficiency of vitamin B12-dependent N5-methyltetrahydrofolate methyltransferase (5-methyltetrahydropteroyl-L-glutamate:L-homocysteine S-methyltransferase, EC 2.1.1.13) and normal adult cells are grown in media containing methotrexate and either N5-methyltetrahydrofolate or N5-formyltetrahydrofolate, not only is the selective toxicity of methotrexate demonstrated, but the advantage of using N5-methyltetrahydrofolate in place of N5-formyltetrahydrofolate is also revealed. The implications and applications of this particular combination in the treatment of human cancer are discussed.

Animals↗
PubMed1975

Vestibular-ocular accommodation reflex in man.

Stimulation of the vestibular system by angular acceleration produces widespread sensory and motor effects. The present study was designed to study a motor effect which has not been reported in the literature, i.e., the influence of rotary acceleration of the body on ocular accommodation. The accommodation of 10 young men was recorded before and after a high-level deceleration to zero velocity following 30 s of rotation. Accommodation was recorded continuously on an infrared optometer for 110 s under two conditions; while the subjects observed a target set at the far point, and while they viewed the same target through a 0.3-mm pinhole. Stimulation by high-level rotary deceleration produced positive accommodation or a pseudomyopia under both conditions, but the positive accommodation was substantially greater and lasted much longer during fixation through the pinhole. It is hypothesized that this increase in accommodation is a result of a vestibular-ocular accommodation reflex.

Accommodation, Ocular↗
PubMed1975

Altered distribution and excretion of N-1-methylnicotinamide in rats with Walker 256 carcinosarcoma.

Levels of nicotinamide and N-1-methylnicotinamide in serum, liver, and kidney as well as renal clearances and 24-hr urine levels of N-1-methylnicotinamide were compared in normal rats and rats bearing Walker 256 tumors. There was no significant difference between normal and tumor-bearing rats with regard to nicotinamide levels. With regard to N-1-methylnicotinamide, tumor-bearing rats had significantly lower serum and liver levels and significantly higher 24-hr urine levels and renal clearances. Walker 256 tumor tissue and liver and kidney from a normal and a tumor-bearing rat were separately examined for S-adenosylmethionine:nicotinamide methyltransferase activity. The specific activity in tumor tissue extract was greater than that in each liver extract, which, in turn, was much greater than the specific activity in each tissue (liver and kidney) from the tumor-bearing rat was equal to the specific activity in the corresponding tissue of the normal rat. S-adenosylmethionine:nicotinamide methyltransferase was obtained with 18-fold purification from a tissue extract of Walker 256 tumor. The enzyme activity required activation by thiols, and maximal activity was observed at pH 8.6. The Km's for the substrates, S-adenosylmethionine and nicotinamide, were 7.0 x 10--3 mM and 0.50 mM respectively. The Ki's for the products, S-adenosylhomocysteine and N-1-methylnicotinamide, were respectively, 25 x 10--3 mM and greater than 5 mM.

Animals↗