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Biomedical subjects

K A Palmer

Publications and source records attributed to K A Palmer.

14 recordsLinked to original sources

A preliminary three-dimensional structure of angiogenin.

A preliminary three-dimensional structure of angiogenin has been computed, based on its homology to bovine pancreatic ribonuclease A. A standard-geometry structure of ribonuclease was first obtained from its x-ray coordinates. The fit of the backbone of angiogenin to that of ribonuclease was then optimized by taking account of amino acid deletions and by minimizing its conformational energy-plus-a-penalty distance function constraining its backbone to that of ribonuclease. Side-chain and backbone dihedral angles were allowed to vary throughout the cycles of energy minimization. In the last stages of minimization, the penalty distance function was removed. A low-energy structure resembling ribonuclease was obtained.

Humans

Characterization of thymidine kinase in L5178Y mouse lymphoma cells.

Thymidine kinase (TK) was isolated from four different cell lines (TK +/+ P4, TK +/- P4.3.4, TK +/- 3.7.2C, and TK -/- P4.3) that represent the genotypes of L5178Y mouse lymphoma cells. TK isolated from each of the different cell lines was characterized with respect to the estimated isoelectric point (pI), temperature sensitivity, estimated substrate dissociation constants (Km), estimated inhibitor constant (Ki), and response to the activator deoxycytidine diphosphate. The characteristics of TK from the different cell lines were compared to determine whether the product of the TK gene was changed by the mutation that produced the TK -/- genotype and reverse mutation to the TK +/- genotype. The results indicate that the TK enzymes isolated from the TK +/+ P4, TK +/- P4.3.4, and TK +/- 3.7.2C cells have similar, if not the same, characteristics. The small amounts of TK associated with TK -/- P4.3 and the mitochondria from TK +/+ P4 had similar characteristics, and both were different in many respects from the TK associated with the TK +/+ P4, TK +/- P4.3.4, and TK +/- 3.7.2C. These results raise a question about whether a structural gene is the target for chemical mutagens in the L5178Y TK +/- assay; however, this can only be answered by the isolation of the TK gene from each of the L5178Y genotypes and determination of the nucleotide sequence.

Animals

Protocols for the dominant lethal test, host-mediated assay, and in vivo cytogenetic test used in the food and drug administration's review of substances in the gras (generally recognized as safe) list.

Protocols are described for the dominant lethal and in vivo cytogenetics test in rats and the host-mediated assay, using Salmonella typhimurium and Saccharomyces cerevisiae in mice, as used by the Food and Drug Administration in its mutagenicity review of substances from the generally recognized as safe (GRAS) list. In addition proctolols are described for in vitro mutagenicity tests with S. typhimurium and S. cerevisiae and for statistical treatment for evaluation of data from dominant lethal tests.

Animals

Cytogenetic studies in rats of cyclohexylamine, a metabolite of cyclamate.

Cyclohexylamine, the major known metabolite of cyclamate, was tested in vivo for possible cytogenetic effects. In rats injected with this metabolite, there was a direct relation between dose concentration and percentage of spermatogonial and bone marrow cells showing chromosomal breaks. Single chromatid breaks predominated with infrequent exchange figures.

Amines

Mutagenic activity of 5 thiazole compounds in the Salmonella/microsome and mouse lymphoma TK+/- assays.

To aid in the selection of chemical candidates for in vivo tests, the mutagenicity of 5 thiazole compounds was evaluated in the Salmonella plate incorporation assay and mouse lymphoma L5178Y TK+/- assay. Two of the compounds, 2-thiazolamine and 3-methyl-5-isothiazolamine, were positive in both assays; and one, thiazole, was negative. With the other 2 compounds the results were nonconcordant: 5-phenyl-2,4-thiazolediamine was negative in the Salmonella assay but positive in the mouse lymphoma assay, and C.I. Basic Red 29 was positive in the Salmonella assay while the response in the mouse lymphoma assay was considered equivocal.

Animals

The mutagenic assay of some hair dye components, using the thymidine kinase locus of L5178Y mouse lymphoma cells.

Five hair dye components were tested for their mutagenicity at the TK +/- locus of L5178Y cells. Three of the components, m-phenylenediamine, 2 nitro-p-phenylenediamine, and 4-nitro-o-phenylenediamine, gave a positive response that was dose related; 2,4-diaminoanisole gave a questionable response; and 2,5-diaminoanisole gave a negative response. The assay was carried out in vitro without metabolic activation during a 24-hr chemical exposure period. It is concluded that further in vivo tests are necessary to establish the safety of the hair dyes.

Animals