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Biomedical subjects

B W Stewart

Publications and source records attributed to B W Stewart.

At least 91 records · Page 5Linked to original sources
PubMed1976

DNA damage and repair in intact animals. Single-stranded regions in rat liver DNA following administration of dimethylnitrosamine.

Rat liver DNA was radioactively labelled by administration of [3H]thymidine following partial hepatectomy. Two weeks later, the rats were treated with the carcinogen, dimethylnitrosamine. DNA was isolated and fractionated by elution from benzoylated DEAE-cellulose with NaCl and caffeine solution. The caffeine-eluted fraction was increased by administration of dimethylnitrosamine. This increase was proportional to the dose of carcinogen injected and persisted for at least 24 h after administration of the carcinogen. These data, together with the results of hydroxyapatite chromatography, suggest that the DNA contains short single-stranded sections associated with much longer regions of native DNA.

Animals↗
PubMed1975

Acute biochemical and morphological effects of N-nitrosomorpholine in comparison to dimethyl- and diethylnitrosamine.

Some biochemical and ultrastructural changes induced in the livers of rats treated with N-nitrosomorpholine are described and compared with parallel observations in rats given dimethyl- or diethylnitrosamine. Hepatotoxic doses of the nitrosamines caused inhibition of incorporation of [14C]leucine into hepatic proteins, accompanied by progressive disaggregation of polysomes which paralleled the known time course of metabolism of each compound. Dimethylnitrosamine (DMN) and N-nitrosomorpholine (NM) inhibited incorporation of [14C]orotate into liver RNA but diethylnitrosamine (DEN) caused a slight stimulation of orotate incorporation. Electron microscopy revealed similar hepatic cytoplasmic changed induced by each nitrosamine, including dilation and degranulation of the rough surfaced endoplasmic reticulum and subsequent increase of the smooth endoplasmic reticulum. Nuclear changes differed with each compound, N-nitrosomorpholine having more marked effects than either dialkyl compound. The results are discussed with particular reference to the metabolism of N-nitrosomorpholine in the liver.

Animals↗
PubMed1971

Effect of a single dose of dimethylnitrosamine on biosynthesis of nucleic acid and protein in rat liver and kidney.

1. Administration of a single dose of dimethylnitrosamine to rats temporarily fed on a protein-deficient diet causes a high incidence of kidney tumours. The effect of such a dose of dimethylnitrosamine (40mg/kg body wt.) on metabolism of nucleic acids and protein in rat liver and kidneys was examined during the week immediately after administration. 2. Incorporation of [(14)C]leucine and [(14)C]orotate into hepatic macromolecules was inhibited within 5h of injection of dimethylnitrosamine, and did not recover for at least 5 days. Interpretation of these results is complicated by the concomitant extensive hepatic necrosis. 3. Renal RNA synthesis was assayed by incorporation of [(14)C]orotate in vivo and measurement of DNA-dependent RNA polymerase activity in vitro. Both systems indicate biphasic inhibition; minimal activity was recorded 9h and 3 days after treatment. Changes in incorporation of [(14)C]leucine into renal protein were similar but less marked. 4. Sucrose-density-gradient analysis of renal cytoplasmic RNA indicated increased synthesis of rRNA 24h after injection of the nitrosamine. The rate of loss of radioactivity from kidney ribosomes pre-labelled with [(14)C]orotate was not modified by dimethylnitrosamine. 5. Dimethylnitrosamine increased incorporation of [(3)H]-thymidine into renal DNA. The three distinct periods of stimulated synthesis observed are discussed, with particular reference to recently published morphological studies of the sequential development of kidney tumours induced by dimethylnitrosamine in protein-depleted rats.

Animals↗
PubMedDate not supplied

Inhibition of topoisomerase II by aurintricarboxylic acid: implications for mechanisms of apoptosis.

Internucleosomal fragmentation of DNA, the most widely used biochemical indicator of apoptosis, is believed to contribute to loss of viability because the nuclease inhibitor, aurintricarboxylic acid, delays or prevents cell death in a range of experimental systems. We report here that auritricarboxylic acid inhibits topoisomerase II in vitro, the concentration required (< or = 0.2 microM) being less than that usually employed in studies of apoptosis. Since topoisomerase II mediates chromatin condensation during apoptosis, the efficacy of ATA in preventing or delaying cell death may not be the result of nuclease inhibition.

Apoptosis↗