PubMed Health⌕ Search

Biomedical subjects

B E Butterworth

Publications and source records attributed to B E Butterworth.

6 recordsLinked to original sources
PubMed1979

The effect of 2,4-diaminotoluene and isomers of dinitrotoluene on unscheduled DNA synthesis in primary rat hepatocytes.

The important industrial chemicals 2,4-dinitrotoluene (DNT) and 2,4-diaminotoluene (DAT) are hepatocarcinogens in rats. Technical grade DNT contains approximately 76% 2,4-DNT, 19% 2,6-DNT, and lesser amounts of the other isomers. The ability of 2,4-DAT, technical grade 2,4-DNT, and the purified isomers 2,3-DNT, 2,4-DNT, 2,5-DNT, 2,6-DNT, 3,4-DNT and 3,5-DNT to damage the DNA of primary rat hepatocytes was examined. Male Fischer-344 rats were perfused in situ, single cell suspensions were obtained after liver dissociation, and cultures of these cells were treated in the presence of 3H-thymidine. Autoradiography was employed to visualize label incorporation following repair of DNA. At the nontoxic (as judged by cell morphology) doses of 1 x 10(-4) M and below, only 2,4-DAT induced a significant response (ie an average greater than 5 grains net/nucleus). The activity seen with 2,4-DAT suggests that damage to the DNA of the hepatocytes may play a role in its carcinogenic activity and is consistent with the proposal that the induction of DNA repair in primary hepatocytes is of value in predicting the activity of aromatic amino compounds. However, the carcinogenic activity of the dinitrotoluenes was not reflected as DNA repair in the isolated hepatocyte, indicating that additional factors involving the whole animal also play a role in the mechanism of action of DNT.

Animals↗
PubMed1976

Inhibition by zinc of rhinovirus protein cleavage: interaction of zinc with capsid polypeptides.

Zinic ions rapidly inhibit virus production in HeLa cells infected with human rhinovirus type 1A and lead to the accumulation of human rhinovirus type 1A precursor polypeptides. The degree to which cleavage of these precursors is inhibited is directly dependent on the quantity of cell-associated zinc. Proteolysis resumes after the removal of zinc-containing medium, and the accumulated viral precursors are cleaved predominantly to stable virus polypeptides. The precursors stabilized at the lowest zinc levels are those that contain capsid protein sequences. Furthermore, added zinc is bound to human rhinovirus type 1A capsids and prevents them from forming crystals. Zinc-resistant mutants display antigenic alterations in coat proteins. These results suggest that zinc complexes with rhinovirus coat proteins and alters them so that they cannot function as substrates for proteases or as reactants in the assembly of the virus particles.

Capsid↗
PubMed1976

Association of the polioviral RNA polymerase complex with phospholipid membranes.

Polioviral RNA polymerase complex, which consists of enzyme, template, and nascent RNA, is membrane bound in vivo. The solubilized RNA polymerase complex associated spontaneously in vitro with phospholipid bilayer membranes (liposomes) of defined composition. The degree of association at 37 degrees C was greater for those membranes that were more fluid, suggesting that the binding involves the interaction of the RNA polymerase complex with the hydrocarbon chains in the interior of the lipid bilayer. The polymerase activity was not enhanced by addition of the lipid; in fact, the addition of some of the longer-chain lipids resulted in up to a 40% inhibition of the polymerase activity. Spin-label electron paramagnetic resonance experiments, which measured the membrane fluidity, and kinetic experiments on the rate of incorporation of tritiated UTP into RNA by the polymerase were performed as a function of temperature. The results indicated that the activity of the polymerase was not affected by the physical state of the phospholipid membrane and that its active site was not intimately associated with the membrane. Analysis of both the viral and host polypeptides associated with the smooth membrane-bound polymerase indicated that X was the primary viral polypeptide present. In addition, host polypeptides of molecular weight 86,000, 62,000, 54,000, and 46,000 were also present. If the membrane was disrupted with detergent, polypeptide X was released from the polymerase activity, suggesting that X may play a role in binding the polymerase to the membrane. In an analogous manner, polypeptide X associated spontaneously with phospholipid membranes to a greater extent than the capsid polypeptides. Analysis of both the host and viral polypeptides associated with the viral RNA polymerase purified by precipitation in 2 M LiCl indicated that host polypeptides of molecular weight 106,000, 38,000, 33,000, and 14,000 were the major constituents, whereas relatively small amounts of the viral polypeptides were present. It was confirmed that of the viral polypeptides found, polypeptide 4 was present in the largest amount.

DNA-Directed RNA Polymerases↗