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G Bailey

Publications and source records attributed to G Bailey.

At least 55 records · Page 3Linked to original sources
PubMed1987

Reduced levels of histones H1o and H1b, and unaltered content of methylated DNA in rainbow trout hepatocellular carcinoma chromatin.

The levels of histone subtypes and DNA methylation of aflatoxin-induced rainbow trout hepatocellular carcinoma and adult liver nuclei were compared. The hepatocellular carcinoma nuclei were enriched in the ubiquitinated species of histone H2A and depleted in histones H1o and H1b. The 5-methylcytosine content and methylation patterns of the vitellogenin genes and the transcriptionally inactive TPG-3 protamine gene were not altered in the trout hepatocellular carcinoma DNA. Thus, undermethylation of DNA is not a general feature of chemically induced tumors in vivo.

5-Methylcytosine↗
PubMed1987

Comparative binding and sequence interaction specificities of aflatoxin B1, aflatoxicol, aflatoxin M1, and aflatoxicol M1 with purified DNA.

The covalent binding of the activated forms of several aflatoxins to N-7 of guanine residues on purified DNA has been studied. The aflatoxins include aflatoxin B1 (AFB1) and two human metabolites, aflatoxicol and aflatoxin M1, along with aflatoxicol M1, a rabbit and trout metabolite. DNA binding studies using tritiated [3H]aflatoxins indicate that equimolar solutions of each aflatoxin upon activation with chloroperoxybenzoic acid readily react to produce covalently bound adducts. These reactions produce alkali-labile sites which can be identified using a simple variation of the Maxam-Gilbert sequencing procedure. Two DNA fragments were exposed to each aflatoxin, and the reaction intensities at 33 guanine residues were determined. As much as 10-fold variation in reaction intensities was observed for various guanyl sites. Data indicate that none of the aflatoxins had identical reaction profiles, although AFB1 and aflatoxicol M1 were similar, as were aflatoxicol and aflatoxin M1. Hence, the frequency with which the various aflatoxin epoxides might damage specific sites critical for tumor initiation in vivo would not be predictable from total covalent binding indices. The frequency of occurrence of modifications at particular sites for AFB1 was also compared with the empirical "rules" established for AFB1 by Misra et al. (Misra, R. P., Muench, K. F., and Humayun, M. Z. (1983) Biochemistry 22, 3351-3359). Identical sites within fragments were compared for each aflatoxin, and the data showed that the attacking frequency for some such sites varied significantly. These results indicate that binding intensity rules based on nearest neighbor nucleotides do not reliably predict guanyl-AFB1 binding frequencies.

Aflatoxin B1↗
PubMed1987

Metabolism and DNA-binding in vivo of aflatoxin B1 in medaka (Oryzias latipes).

1. The medaka (Oryzias latipes), a small aquarium fish, was shown to possess the capacity to rapidly activate AFB1 in vivo at 25 degrees C to intermediates that bind to DNA. 2. The dose-response for in vivo AFB1-DNA binding was linear over the range 70-550 micrograms AFB1/kg body weight. 3. Maximum binding occurred within the first 24 hr after i.p. injection of [3H]AFB1, followed by a rapid loss of adducts. 4. Aflatoxicol (AFL) and unreacted AFB1 were found by HPLC analysis to be the major products excreted into water after AFB1 exposure, with excretion of AFL as early as 2 min after AFB1 injection. 5. These studies show that medaka possess enzymatic systems similar to rainbow trout (Salmo gairdneri) for biotransformation of AFB1 to the epoxide and to other phase I and phase II metabolites.

Aflatoxin B1↗
PubMed1987

Initiation, promotion, and inhibition of carcinogenesis in rainbow trout.

The identification of etiological agents in feral fish neoplasia epizootics has been hampered in part by the lack of suitable fish models, and complicated by the likely existence of environmental agents which can act to stimulate or reduce population responses to genotoxin insult. The response of fish to tumor inhibitors and promoters, and the underlying mechanisms of modulation, have been studied in the rainbow trout model. Dietary treatment of trout with the compounds indole-3-carbinol (I3C), beta-naphthoflavone (BNF), or the polychlorinated biphenyl (PCB) complex Aroclor 1254, before and during exposure to aflatoxin B1 (AFB1), was shown to reduce the final incidence of hepatocellular carcinoma after 12 months, compared to fish receiving AFB1 only. By contrast, treatment of trout with BNF or I3C following AFB1 initiation led to a significant enhancement of ultimate tumor response. Similarly, simultaneous treatment of trout with PCB and the carcinogen N-nitrosodiethylamine led to syncarcinogenic enhancement, rather than inhibition, of tumor response. Mechanisms of inhibition of AFB1 carcinogenesis by PCB, BNF, and I3C were investigated. PCB and BNF, but not I3C, are known to be strong inducers of trout cytochrome P448 and associated activities. Dietary induction by BNF or PCB was shown to be accompanied in isolated hepatocytes by considerably altered AFB1 metabolism, and by significantly reduced rates of DNA adduct formation for all three agents. All agents differentially altered in vivo AFB1 pharmacokinetics, enhanced bile elimination of AFB1 as the aflatoxicol-M1 glucuronide, and significantly reduced peak levels of liver DNA adduct formation. No effects were seen on repair of AFB1-DNA adducts, which was very slow in trout.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Non-centrifugal plasma collection using cross-flow membrane plasmapheresis.

A prototype of a cross-flow membrane plasmapheresis system was tested for its safety and efficacy in normal donors. 550 ml of plasma can be harvested in less than 1 h. The procedure appears to be safe for the donor. No significant alterations in donor hematological, coagulation, or biochemical values were obtained after the procedure compared to the predonation levels. Changes in the classical and alternate complement pathways were studied serially by analysis of functional hemolytic titers, C3 and C4 levels, and C3 and factor B cleavage products. No firm evidence of complement activation by the polysulfone filtration cell membrane was found.

Adult↗
PubMed1983

Long-term follow-up of donors cytapheresed more than 50 times.

11 volunteers who had donated white blood cells or platelets more than 50 times over a 5- to 9-year period were studied to determine whether any adverse consequences of many cytaphereses could be detected. Among the donors no significant differences were found in 18 hematological and biochemical parameters when compared to a group of age- and sex-matched nondonor controls. Despite extensive cumulative lymphocyte losses sustained by these donors, the ratio of T, B, helper and suppressor cells has been maintained within the normal range. No detrimental effects of multiple cytapheresis on the donors' health has been demonstrated to date.

Adult↗
PubMed1982

Mechanisms of dietary modification of aflatoxin B1 carcinogenesis.

Trout were fed a range of dietary components which altered their carcinogenic response to aflatoxin B1 (AFB1). Dietary protein at levels substantially exceeding nutritional requirements were synergistic with AFB1. Cyclopropene fatty acids (CPFA) were carcinogenic when fed alone at 20 or 55 ppm, and synergistic when fed with AFB1. In contrast, several flavonoid and indole compounds, especially beta-naphthoflavone (beta-NF) and indole-3-carbinol, inhibited the carcinogenic response when fed prior to and along with AFB1. The mechanisms by which some of these dietary factors modulate AFB1 carcinogenesis were investigated. Dietary beta-naphthoflavone was shown to substantially induce the levels of mixed function oxidase (MFO) activities assayed in vitro. These changes were accompanied by alterations in AFB1 metabolism and binding in freshly isolated hepatocytes. AFB1 incubated in hepatocytes freshly isolated from fish fed beta-NF diet was metabolized more rapidly, showed enhanced rates of detoxication reactions, and decreased accumulation of AFB1-DNA adducts compared to control hepatocytes. These results suggest that beta-NF inhibits AFB1 carcinogenesis at least in part by altering MFO activities such that detoxication is enhanced and initial DNA damage by AFB1 is reduced. In contrast, high dietary protein is a synergist for AFB1 carcinogenesis, and this appears to occur primarily by enhancing the transformation probability for AFB1-initiated genome damage. Fish treated with AFB1 as embryos and then reared on high protein diets had substantially higher incidences of hepatocellular carcinoma (86%) than similarly treated fish fed normal protein diet (44%) or high protein controls without AFB1 exposure (0-2%). The synergistic behavior of dietary CPFAs also appears to partially involve enhanced transformation following DNA damage by AFB1. Fish exposed as embryos to AFB1 and then fed CPFA-containing diets are known to show promotion effects similar to the high protein results (Hendricks, J.D., Proc. 11th Int. Symp. of the Princess Takamatsu Cancer Research Fund, in press.) However, factors other than promotion are involved in the synergism between CPFA and AFB1. Preliminary studies indicate that dietary CPFAs repress MFO activities and depress DNA damage by AFB1 in vitro. If this occurs in vivo, then the net synergistic effect of dietary CPFAs would involve depression of initial AFB1-induced DNA damage, but highly efficient promotion of transformation from the remaining lesions.

Aflatoxin B1↗
PubMed1981

A comparison of the response to hyperthermia of murine haemopoietic stem cells (CFU-S) and L1210 leukaemia cells: enhanced killing of leukaemic cells in presence of normal marrow cells.

When the clonogenic survival of mouse haemopoietic stem cells (CFU-S) and leukaemia L1210 cells growth as ascites tumours are compared after being heated in vitro and assayed in vivo by spleen-colony assay, there is no significant difference in the terminal slopes of the survival curves. The shoulders of the survival curves differ, but this may be explained by differences in cell kinetics. By contrast, L1210 leukaemic marrow cells are considerably more susceptible to the lethal effects of hyperthermia (43 degrees C) than either normal marrow stem cells or L1210 leukaemic cells grown as ascites tumours. Moreover, the killing of L1210 ascites cells by hyperthermia can be enhanced by heating L1210 ascites cells with an equal number of normal marrow cells, or as upernatant removed from heated marrow cells. Most cells in lukaemic marrow are normal, and it is postulated that the increased thermal sensitivity of L1210 cells in leukaemic marrow is caused by diffusible factors (e.g. lysosomal enzymes) released by heating normal marrow cells.

Animals↗
PubMed1981

Phospholipase activity in skin after application of phorbol esters and 3-methylcholanthrene.

Topical administration of the promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), is accompanied by an increased incorporation of [3H]arachidonic acid into mouse skin and a very significant activation of epidermal cell membrane phospholipase A2 without affecting intracellular acid phospholipase. Similar enhancement in epidermal cell phospholipase A2 was observed after application of phorbol-12,13-didecanoate or 3-methylcholanthrene to mouse skin. A small but significant increase in phospholipase A2 activity is also seen after application of the nonpromoter irritant, acetic acid. The elevated levels of the prostaglandins observed in mouse skin after topical application of promoters are probably triggered by the activation of this membrane enzyme.

Animals↗
PubMed1979

Myocardial function in feline endotoxin shock: a correlation between myocardial contractility, electrophysiology, and ultrastructure.

The nature of the myocardial depression observed in patients with septic shock, and in animals late in shock induced by endotoxin, is still under examination. These studies, in cats and kittens administered an LD80 dose of E coli endotoxin, were designed to examine the relationship between changes in myocardial contractility, in cellular electrophysiology and in ultrastructural morphology. There was no difference between tension developed in vitro by cardiac muscle removed from cats five hours after endotoxin administration and from cats not administered endotoxin. There was also no difference in their responses to calcium chloride or to anoxia. The action potential characteristics of ventricular muscle isolated from endotoxin treated cats were also not different from control, and ultrastructural damage was minimal and not extensive. Endotoxin (100 microgram/ml) had no effect on cardiac muscle in vitro, even after a one-hour contact time. It is concluded that the integrity of the myocardium is maintained even late in shock and that endotoxin has no direct effects on the heart.

Action Potentials↗
PubMed1975

Relative numbers of human globin genes assayed with purified alpha and beta complementary human DNA.

Purified alpha and beta globin complementary DNAs (cDNAs) have been separated from total radioactively labeled human globin cDNA using mRNA purified from liver of a hydrops fetalis (alpha thalassemia). The beta cDNA hybridizes to the hydrops fetalis mRNA while the alpha cDNA remains single-stranded. the purified alpha and beta cDNAs were assayed for their purity by their hybridization to mRNA prepared from reticulocytes of nonthalassemia, alpha thalassemia, and beta thalassemia subjects. The results indicate that the separated cDNAs are selective in hybridization to alpha or beta globin mRNAs, respectively. The previously reported deficiency of globin mRNA in thalassemia cells has been confirmed with these purified cDNAs. The purified alpha and beta cDNAs were hybridized to cellular DNA to non-thalassemia, beta+ thalassemia, and hydrops fetalis (alpha thalassemia) DNA. The alpha cDNA hybridized to hydrops fetalis liver DNA to a much lower extent that beta cDNA, confirming the previously reported deletion of alpha globin genes in hydrops fetalis. By contrast, both the alpha and beta DNA probes hybridized to the same extent to spleen DNA from non-thalassemia and from beta+ thalassemia patients. Between two and five globin genes in non-thalassemia and beta+ thalassemia DNA hybridize to beta cDNA and one to five to alpha cDNA. These studies indicate that in beta+ thalassemia, there is no detectable deletion in beta globin genes. The genetic defect in beta+ thalassemia appears to be due to either repression of transcription of beta globin genes or abnormal processing of beta globin mRNA.

Bone Marrow↗
PubMed1974

Observations on the use of solid-phase-coupled antibodies in the radioimmunoassay of human placental lactogen.

A detailed comparative assessment was made of the use of solid-phase-coupled antibodies in radioimmunoassay, by using an assay for human placental lactogen as a model system. The major advantages of the solid-phase technique are: (1) in common with the use of a second antibody, it is universally applicable; (2) separation can be carried out rapidly; (3) in contrast with some other techniques, the separation of antibody-bound and free antigen is virtually complete. The disadvantages when compared with other procedures are: (1) a considerable proportion of the antibody may be lost during the initial coupling reaction; (2) the tubes must be continuously mixed during incubation, and much effort is expended in removing and replacing the caps; (3) there is a decrease in the apparent affinity constant of the antibody after coupling, which is reflected in a lower sensitivity of the assay system. It is concluded that solid-phase antibodies are of greatest value in those systems in which the supply of antiserum is abundant, and in which the achievement of high sensitivity is not a requirement.

Adsorption↗