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Biomedical subjects

D P Cooper

Publications and source records attributed to D P Cooper.

44 records · Page 3Linked to original sources
PubMed1984

Enhanced repair of O6-alkylguanine in mammalian tissues.

N-nitroso compounds and related alkylating agents react with several nucleophilic sites in DNA. One of the products, O6-alkylguanine, may be responsible for the carcinogenic effects of such agents as it can mispair with thymine during DNA replication, thereby affecting the integrity of the genome and consequently the repair of this lesion could be an important determinant in carcinogenesis. The use of both in vivo and in vitro procedures for the assay of the activity of this repair system have shown that it can be enhanced in rat liver by treatment with a variety of agents while in other species, the system is not only less effective but does not appear to respond to such treatments. Differences in the capacity and inducibility of this repair system may be related to the susceptibility of different species to tumour induction by chronic administration of nitrosamines.

2-Acetylaminofluorene↗
PubMed1982

Effect of acute doses of 2-acetylaminofluorene on the capacity of rat liver to repair methylated purines in DNA in vivo and in vitro.

Male Wistar rats were given various doses of 2-acetylaminofluorene (AAF) at doses of 0.74, 2.22, 6.67, or 20 mg/kg i.p. 24 hr before administration of [14C]dimethylnitrosamine (1 or 2 mg/kg i.p.). Analysis of liver DNA isolated from animals killed 5 hr later showed variations between groups treated with different amounts of AAF in the amounts of 3-methyladenine, 7-methylguanine, and O6-methylguanine (O6-mGua). However, the relative amounts of these products were unchanged by AAF pretreatment except after 20 mg/kg when the reduced O6-mGua:7-methylguanine ratio indicated enhanced O6-mGua repair. Specific enhancement of O6-mGua repair was also found 5 hr after administration of [14C]methylnitrosourea (11.5 mg/kg) to animals pretreated with AAF (20 mg/kg), while the amounts of O6-mGua in liver ribosomal RNA afer [14C]dimethylnitrosamine were unaffected by this AAF dose. Pretreatment of rats with AAF 29 hr earlier increased the capacity of cell-free liver extracts to remove O6-mGua from [3H]methylnitrosourea-methylated DNA in vitro. The increase was detectable after 2.22 mg/kg and reached a maximum 3.5-fold increase after AAF, (60 mg/kg). 7-Methylguanine and 3-methyladenine-DNA glycosylase activities were also increased, but this was independent of the dose of AAF. AAF pretreatment produced a slight (3- to 4-fold) increase in incorporation of [3H]thymidine or labeled one-carbon breakdown products of [14C]dimethylnitrosamine into liver DNA which appeared to parallel in vitro O6-mGua repair enhancement, but the increased [3H]thymidine uptake was statistically significant only after the 60-mg/kg dose.

2-Acetylaminofluorene↗
PubMed1967

A comparative study on the fine structure of the basalar muscle of the wing and the tibial extensor muscle of the leg of the lepidopteran Achalarus lyciades.

Basalar and tibial extensor muscle fibers of Achalarus lyciades were examined with light and electron microscopes. Basalar muscle fibers are 100-150 micro in diameter. T-system membranes and sarcoplasmic reticulum make triadic contacts midway between Z lines and the middle of each sarcomere. The sarcoplasmic reticulum is characterized by a transverse element situated among myofilaments halfway between Z lines in every sarcomere. The morphology of Z lines, hexagonal packing of thin and thick myofilaments, and thin/thick myofilament ratios are similar to those of fast-acting insect muscles. Tibial extensor muscle fibers are 50-100 micro in diameter. Except for a lack of the transverse element, the T system and sarcoplasmic reticulum are similar to those of basalar muscle. Wavy Z lines, lack of a hexagonal packing of myofilaments, and larger thin/thick myofilament ratios are similar to those of other postural muscles of insects. The morphology of basalar and tibial extensor muscle is compared to that of other insect muscle with known functions, and reference is made to the possible contribution of the transverse element of sarcoplasmic reticulum in basalar flight muscle to speed and synchrony in this muscle.

Animals↗
PubMedDate not supplied

The E. coli ogt gene.

Explore the source record for details and available documents.

Alkyl and Aryl Transferases↗
PubMedDate not supplied

DNA repair: kinetics and thresholds.

DNA damage is a critical factor in the initiation of chemically induced toxicities (including cancer), and the repair of this damage represents the cell's first line of defense against the deleterious effects of these agents. The various mechanisms of DNA repair are reviewed briefly and the actions of the DNA repair protein O6-alkylguanine DNA alkyltransferase (ATase) are used to illustrate how DNA repair can protect cells against alkylating agent-induced toxicities, mutagenesis, clastogenesis, and carcinogenesis. The effectiveness of this repair protein can be measured based on its ability to deplete levels of its promutagenic substrate O6-methylguanine (O6-meG) in the DNA of cells. These studies reveal that the repair of O6-meG from DNA occurs heterogeneously, both intra- and intercellularly. Even in cells that repair O6-meG hyperefficiently, certain regions of chromatin DNA are repaired with difficulty, and in other regions they are not repaired at all; most likely this lack of repair is a result of the location of the lesion in the DNA sequence. When individual cells are compared within a tissue, some cells are clearly repair deficient, because the O6-meG can persist in DNA for many weeks, whereas in other cells, it is removed within a matter of hours. The role of these repair-deficient cells as targets for alkylating agent induced carcinogenesis is considered. The mechanisms of the homeostatic control of DNA repair function in mammalian cells are not yet well understood. Because there are now indications of the mechanisms by which the level of DNA damage may be sensed (and so influence the activity of the ATase repair protein), this is an important area for future study.

Alkylating Agents↗
PubMedDate not supplied

Glutathione S-transferase M1, T1 and P1 polymorphisms and bladder cancer risk in Egyptians.

Previous studies suggest that bladder cancer risk may vary with GST genotype but these results are inconsistent. The aim of this study was to explore whether GSTM1, GSTT1 and GSTP polymorphisms were associated with increased bladder cancer risk in an Egyptian population. GSTM1, GSTT1 and GSTP1 genotype frequencies were determined in bladder cancer cases (n=72) and healthy controls with no history of malignancies (n=82) using PCR-based techniques. The GSTT1*2 genotype was particularly associated with increased risk (OR 2.71, 95%CI 1.27-5.73) and the GSTM1*2 genotype to a lesser extent (OR 1.63, 95%CI 0.85-3.10). 18.1% of cases but only 7.3% of controls were GSTP1*B*B homozygotes (OR 2.38, 95%CI 0.83-6.87). The presence of two or more a priori at-risk genotypes was associated with increased bladder cancer risk (OR 2.42; 95%CI 1.47-3.97). These results suggest that polymorphisms in the GST genes are associated with increased risk of bladder cancer among Egyptians.

Adult↗