fenretinide has been researched along with Leukemia-L5178* in 2 studies
2 other study(ies) available for fenretinide and Leukemia-L5178
Article | Year |
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Lack of genotoxicity of the cancer chemopreventive agent N-(4-hydroxyphenyl)retinamide.
As part of the preclinical drug safety evaluation of the cancer chemopreventive agent N-(4-hydroxyphenyl)retinamide (HPR) in vitro and in vivo tests were conducted to assess its genotoxic activity. Negative findings from HPR testing were demonstrated in the Ames Salmonella/microsomal activation test, the L5178Y mouse lymphoma assay, and a rat bone marrow cytogenetics study. These data imply that HPR lacks the ability to induce point mutations or chromosomal aberrations, and is therefore not genotoxic. Limited testing of retinyl acetate in the Ames test, the L5178Y mouse lymphoma assay, and the primary rat hepatocyte/DNA repair assay yielded consistently negative results. These findings and previously published results concerning retinoid genotoxicity are discussed. Topics: Animals; Antineoplastic Agents; Bone Marrow Cells; Chromosome Aberrations; Cricetinae; Cytogenetics; Diterpenes; Fenretinide; Leukemia L5178; Male; Mesocricetus; Mice; Mitosis; Mutagenicity Tests; Rats; Retinoids; Retinyl Esters; Salmonella typhimurium; Tretinoin; Vitamin A | 1985 |
Alterations of drug-induced toxicity in the mouse lymphoma assay by a rat hepatic microsomal metabolizing system (S-9).
Large differences in induced cellular toxicity were observed in the presence or absence of a rat liver microsomal metabolizing system (S-9) during drug testing in the mouse lymphoma assay. After studying the fate of three drugs in this test system, several mechanisms were demonstrated whereby S-9 reduced cellular toxicity. For N-(4-hydroxyphenyl)retinamide (HPR), fenoctimine sulfate and methyl palmoxirate, the drug concentrations (EC50) in the presence of S-9 were, respectively, 11.5, 14.3 and 4.1 times the concentrations required to achieve comparable levels of toxicity in the absence of S-9. HPR was metabolized by the S-9 and sequestered in the microsomal membranes. This was associated with a marked reduction in the cellular accumulation of the drug. The reduced toxicity of fenoctimine sulfate in the presence of S-9 was associated with extensive biotransformation to polar metabolites. This was accompanied by a reduction of radioactivity associated with the cells from 5.7% to 0.4% of the administered drug. Methyl palmoxirate was rapidly converted to its acid, palmoxirate, by horse serum enzymes present in the treatment medium. This provides an example of metabolism by a test system component other than the S-9 or lymphoma cells. The reduced toxicity of this drug in the presence of S-9 was attributed to further metabolism of palmoxirate and a reduction of the proportion of total radioactivity associated with the cells from 3.1% to 0.4%. These results emphasize the need for pilot toxicity studies, especially when components of the test system are varied, to assess the effect of drug concentration on the toxic response.(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Animals; Biotransformation; Cell Division; Cell Line; Cells, Cultured; Epoxy Compounds; Ethers, Cyclic; Fenretinide; Leukemia L5178; Leukemia, Experimental; Male; Mice; Microsomes, Liver; Mutagenicity Tests; Mutagens; Piperidines; Propionates; Rats; Tretinoin | 1984 |