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Biomedical subjects

S H Cox

Publications and source records attributed to S H Cox.

16 recordsLinked to original sources
PubMed1986

Biological availability of nickel arsenides: cellular response to soluble Ni5As2.

Particulate Ni5As2 has been shown to be highly cytotoxic and carcinogenic. By measuring the solubility of Ni5As2 particles in a variety of aqueous solutions, we have determined that particulate Ni5As2 that might be produced during oil-shale retorting could be mobilized to the environment and made available to the cells of living organisms, including humans. Ni5As2 was five times more soluble in ground water taken from aquifers surrounding a major oil-shale source in Colorado, U.S.A., than in distilled water. It was also two times more soluble in oil-shale product water from an above-ground retort than in distilled water. Thus, it is possible that Ni5As2 could be solubilized and mobilized to the environment by the flooding of abandoned in situ retorts with ground water or by the disposal of oil-shale product water by spraying it on spent shale beds. Particulate Ni5As2 was found to be 12 times more soluble in culture growth medium than in distilled water, and much more soluble in solutions of amino acids, inorganic salts, organic constituents of culture medium, and 15% calf serum. These observations suggest Ni5As2 particles in airborne dust would be dissolved when they came in contact with the biological fluids of the lung and gastrointestinal tract. The availability to cells of the soluble products of Ni5As2 was demonstrated by measuring its effects on cell proliferation. As little as 1 ppm soluble Ni5As2 retarded Chinese hamster (CHO) cell proliferation in culture, and 4 ppm resulted in cell death. Flow cytometry measurements indicated there was a preferential cytotoxic effect on S-phase cells. Despite this, many cells survived to form colonies, causing concern that Ni5As2 might cause genetic damage that could be passed on to future cell generations. This did not appear to be the case, however, for no mutations could be detected at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus in cells that survived the cytotoxic effects. This suggests that Ni5As2 carcinogenesis might be caused by epigenetic rather than mutagenic mechanisms.

Animals↗
PubMed1985

A coordinate relationship between the GALK and the TK1 genes of the Chinese hamster.

Chinese hamster cells in culture were treated with various concentrations of thymidine, 5-bromodeoxyuridine, trifluorothymidine, and 2-deoxy-D-galactose. Selection was made for deficiencies in the activities of galactokinase and thymidine kinase. Selection in the presence of thymidine, 5-bromodeoxyuridine, and trifluorothymidine was expected to produce clones deficient in thymidine kinase only, whereas those deficient in galactokinase were expected to be selected in the presence of 2-deoxy-D-galactose. However, it was found that clones growing in the presence of these inhibitors were frequently deficient in both enzymes. Or if a clone was deficient in only one, the deficiency frequently was not expected according to the selection procedure. This indicates some sort of coordinate relationship between the two gene loci, GALK and TK1, which specify galactokinase and thymidine kinase, respectively. GALK and TK1 are linked in all primates and rodents in which linkage determinations have been made. It is therefore probable that this linkage has been conserved for a long period of time. It is suggested that the apparent relationship between the two genes shown by the data presented here, as well as by others, supports the conclusion that linkage has been conserved by natural selection and is therefore not fortuitous.

Animals↗
PubMed1984

Thymidine-kinase activity of cultured cells from individuals with inherited galactokinase deficiency.

Cells of a person homozygous for galactokinase deficiency and of her heterozygous parents were found to be deficient in the enzyme thymidine kinase. The decrease in thymidine-kinase activity may be the result of a qualitative alteration in the enzyme molecule. This is reflected in the apparent alteration in the sensitivity of the enzyme to trifluorothymidine. It is suggested that this relationship between the galactokinase and thymidine kinase is not fortuitous but a reflection of their interdependence as found previously in the Chinese hamster.

Alleles↗
PubMed1980

Mutation of Chinese hamster cells by near-UV activation of promutagens.

A tissue-culture assay for mutagenesis and cytotoxicity incorporating near ultraviolet (NUV) light activation of polyaromatic hydrocarbons (PAH) has been developed. Cultures of Chinese hamster cells (line CHO) growing in suspension culture were inoculated with benzo[a]pyrene (B[a]P), 7,12-dimethylbenzanthracene (DMBA) of shale-oil retort-water and exposed to light from a high-pressure mercury lamp fitted with a Corning NUV bandpass filter. This light source both permitted activation of PAH and the shale-oil water and preculded detectable damage to DNA. Neither the PAH nor the NUV alone had any effect on cell survival or mutation frequencies but the chemicals plus NUV were extremely effective in producing mutations to 6-thioguanine resistance (hgprt gene).

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1976

Prophage induction and inactivation by UV light.

Analysis of the induction curves for UV light-irradiated Haemophilus influenzae lysogens and the distribution of pyrimidine dimers in a repair-deficient lysogen suggests that one dimer per prophage-size segment of the host bacterial chromosome is necessary as a preinduction event. The close correlations obtained prompted a renewed consideration of the possibility that direct prophage induction occurs when one dimer is stabilized within the prophage genome. The host excision-repair system apparently functions to reduce the probability of "stabilizing" within the prophage those dimers that are necessary for induction and inactivation. The presence of the inducible defective prophage in strain Rd depresses the inducibility of prophage HP1c1.

Bacteriophages↗
PubMed1973

DNA replication of induced prophage in Haemophilus influenzae.

DNA synthesis during transition from the lysogenic state to the lytic cycle and throughout the latter has been studied in Haemophilus influenzae BC200 (HP1c1). Following exposure to ultraviolet light, there is a 30-min delay in DNA synthesis after which there is a rapidly increasing rate of phage DNA synthesis. The phage genome is replicated without extensive utilization of segments or of breakdown products of the bacterial chromosome. The mode of phage DNA replication was investigated by zonal sedimentation of labeled DNA in 5 to 20% neutral and alkaline sucrose gradients. Tritiated thymidine, incorporated during a 2-min pulse given at 38 min, chases rapidly into DNA, sedimenting like linear DNA of approximately 2 x 10(8) daltons, and then, at the expense of label in this peak, chases into slower-sedimenting phage DNA (2 x 10(7) daltons). The fast-sedimenting, rapidly labeled DNA satisfies certain criteria for being a concatenated replicative intermediate. Observations in the electron microscope revealed linear concatemers in the faster-sedimenting material and circular phage-sized DNA in the slower-sedimenting DNA. When induced cells are gently lysed with lysozyme and Brij 58 to maintain DNA-membrane associations and sedimented in neutral sucrose over a cesium chloride shelf, the concatemer is found with the cell-membrane-wall complex. Membrane-associated label chases to membrane-free material sedimenting like deproteinized HP1c1 DNA. When membrane-associated DNA from the cesium chloride shelf is deproteinized and resedimented in neutral sucrose, the sedimentation profile reveals that sedimentation rates of labeled DNA from this complex are indicative of sizes ranging from 2 x 10(8) daltons down to phage-sized pieces of 2 to 3 x 10(7) daltons. A model is presented which places HP1c1-DNA replication on the cell membrane where a concatemer of phage DNA is synthesized and subsequently degraded to phage-equivalent DNA. Phage-equivalent DNA is then either released from the membrane for packaging or is packaged while still membrane associated. Thus, the cell membrane is not only the site of DNA replication during which phage DNA is synthesized in multiple phage-equivalent concatemers but it is also the site at which these concatemers are selectively reduced to phage-sized pieces.

Bacteriophages↗
PubMed1970

Radiation sensitivity of Haemophilus influenzae: a composite response.

The survival of ultraviolet (UV)-irradiated cultures of Haemophilus influenzae Rd is determined by at least two responses: (i) excision-repair ability and (ii) UV-induced cell lysis. An UV-resistant mutant, BC200, has the same capabilities as the wild type, Rd, for excising dimers but does not exhibit lysis. Lytic response is dose-dependent. Relative to the wild type, a lower dose of UV causes lysis of a UV-sensitive mutant, BC100, which is incapable of excising thymine dimers. A lytic protein is present in cultures undergoing lysis. Synthesis of this protein is initiated 45 to 60 min after irradiation. Lysis appears to be due to derepression of a defective prophage which codes for an endolysin-like lytic enzyme.

Bacterial Proteins↗