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J J Clarke

Publications and source records attributed to J J Clarke.

8 recordsLinked to original sources
PubMed2006

A compilation of two decades of mutagenicity test results with the Ames Salmonella typhimurium and L5178Y mouse lymphoma cell mutation assays.

As previously reported [Cameron, T. P., Rogers-Back, A. M., Lawlor, T. E., Harbell, J. W., Seifried, H. E., and Dunkel, V. C. (1991) Gentoxicity of multifunctional acrylates in the Salmonella/mammalian-microsome assay and mouse lymphoma TK+/- assay. Environ. Mol. Mutagen. 17, 264-271], the National Cancer Institute (NCI) shares the responsibility of selecting the most significant chemicals for carcinogenicity testing by the National Toxicology Program (NTP) and has used data from Salmonella and mouse lymphoma mutagenicity assays to aid in the selection and prioritization of chemicals to be further evaluated in chronic 2 year rodent studies. In addition, a number of antineoplastic and anti-AIDS drugs in preclinical evaluation were tested for the NCI's Division of Cancer Treatment Toxicology Branch. In the NCI/NTP chemical selection process, it is no longer necessary to test chemicals prior to sending them to the NTP so the NCI program has ceased performing mutagenicity tests. Some of the testing data has been made available in summary form in the Chemical Carcinogenisis Research Information System (CCRIS), which is searchable on the NLM TOXNET system. The limitations in using this source are that only summary results are available and many negative test results are not included. A summary table that presents the results for each compound is provided in the Appendix with raw data provided in the Supporting Information. The Appendix table contains the compound name, CAS number, and a summary of the data from the Ames test and the mouse lymphoma assay.

Animals↗
PubMed2001

Re-evaluation of the mutagenic potential of quinacrine dihydrochloride dihydrate.

Quinacrine has been used for voluntary female non-surgical sterilization for its ability to produce tubal occlusion. Safety issues regarding quinacrine have been raised because it has been shown to intercalate with DNA. Therefore, safety issues need to be resolved by appropriate toxicology studies to support a review for human transcervical use. Such toxicology studies include mutagenicity assays. Here we report an evaluation of the genotoxicity of quinacrine dihydrochloride dihydrate (QH) using a battery of assays. In the bacterial mutagenicity assay, QH was strongly positive in Salmonella typhimurium tester strain TA1537 with and without S9-activation and in S. typhimurium tester strain TA98 with S9-activation; QH was also strongly positive in Escherichia coli WP2 uvrA without S9-activation. QH was not mutagenic in S. typhimurium tester strains TA100 and TA1535 with and without S9-activation. QH was mutagenic in the mouse lymphoma assay in the absence of S9-activation. QH was clastogenic in Chinese hamster ovary (CHO) cells, with and without S9-activation. QH was negative for polyploidy in the same chromosome aberration test. Using a triple intraperitoneal injection treatment protocol in both male and female mice, QH was negative in the in vivo mouse micronucleated erythrocyte (micronucleus) assay. These results confirm that QH is mutagenic and clastogenic in vitro and suggest a potential risk to human health due to QH exposure after intrauterine exposure.

Animals↗
PubMed2001

Genotoxicity of iron chelators in L5178Y mouse lymphoma cells.

To further study the mechanism of observed iron mutagenicity and cellular toxicity, a number of different iron chelators were evaluated to select a compound that was not mutagenic and had limited toxicity to mouse lymphoma cells. A series of iron chelators including those used clinically, those under development for clinical applications, and those used in nonclinical applications were evaluated. The mutagenic activity of the iron chelators was assessed in L5178Y mouse lymphoma cells. Eight of the 12 iron chelators that were tested induced mutagenic responses both with and without the addition of S9. Among those chelators used clinically or developed for clinical use, the only compound that did not induce a mutagenic response was the starch deferoxamine conjugate. In contrast, deferoxamine mesylate showed the highest toxicity in this group of chemicals and the concentrations leading to toxicity and mutagenicity between the activated and nonactivated assays were not significantly different. The other three chelators that were not mutagenic were Na2EDTA, phytic acid, and ferrozine.

Animals↗
PubMed1999

Alcohol problems and intellectual disability.

The present paper discusses some of the difficulties in working with people with an intellectual disability and an alcohol problem, and draws on the sparse literature about alcohol problems in people with intellectual disability. Four individuals drawn from the current clinical case loads of medical practitioners in UK community intellectual disability services are described. Some suggestions for staff training, patient education and health promotion, and therapeutic approaches are made.

Adult↗
PubMed1978

Design of iron (III) chelates in oral treatment of anemia: solution properties and absorption of iron (III) acetohydroxamate in anemic rats.

The design and use of iron(III) chelates in the oral treatment of iron-deficiency anemia is discussed in terms of the following criteria: (1) the ability of a chelate to exist as a monomeric species even at physiological pH values, (2) the rate of transfer of iron from the chelate to the iron-transporting protein-apotransferrin, (3) the rate of depolymerization of ferric citrate polymer by the free ligand, and (4) its nontoxicity and ability to regenerate hemoglobin levels in anemic rats. Detailed species distribution studies, stability constants, and kinetic data for iron(III) acetohydroxamate (criteria 1-3 above) show that it remains monomeric at physiological pH values and undergoes very rapid iron transfer with apotransferrin. Detailed animal studies show a significant increase in regeneration of hemoglobin in rats fed 2 ml of 4 mM Fe(III) acetohydroxamate daily when compared to rats fed similarly with Fe(III) citrate. A strong potential is thus indicated for Fe(III) acetohydroxamate as a source of iron in the anemic animal.

Administration, Oral↗