Isolation of a human lymphoblastoid line heterozygous at the thymidine kinase locus: possibility for a rapid human cell mutation assay.
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Acridines↗
Biomedical subjects
H L Liber
Publications and source records attributed to H L Liber.
Quantitative forward mutation assay in Salmonella typhimurium using 8-azaguanine resistance as a genetic marker.
We have developed a quantitative forward mutation assay using Salmonella typhimurium, in which resistance to the purine analog 8-azaguanine is used as a genetic marker. We present the assay protocol, the concentration-dependent toxicity and mutagenicity of five known mutagens (N-methyl-N'-nitro-N-nitrosoguanidine, ICR-191, 9-aminoacridine, dimethylnitrosamine, and benzo[a]pyrene), and reconstruction experiments testing the assay for possible bias. The relative merits of forward versus reverse mutation assays are discussed.
Azaguanine↗
Relative sensitivities of forward and reverse mutation assays in Salmonella typhimurium.
Forward mutation to 8-azaguanine resistance and reverse mutation to histidine prototrophy were measured in Salmonella typhimurium after treatment with 16 mutagens of both base-substitution and frameshift classes. The two approaches were found to be equisensitive for all 16 mutagens--i.e., induction of significant mutation occurred at similar concentrations in the forward mutation assay and in the most sensitive of the five Ames tester strains.
Animals↗
Alkyl methane sulfonate mutation of diploid human lymphoblasts and Salmonella typhimurium.
Concentration dependence of mutation in equigenerational exposures to methyl, ethyl, propyl, and butyl methanesulfonates has been determined in diploid human lymphoblasts and Salmonella typhimurium. Forward mutation was measured at the hypoxanthine guanine phosphoribosyltransferase locus in human lymphoblasts and at the putative guanine phosphoribosyltransferase locus in S. typhimurium. Reverse mutation at the his G46 locus was also measured in S. typhimurium. This analysis and previous reports support the conclusion that S. typhimurium and mammalian cells are essentially equisensitive to the mutagenic effects of ethyl methanesulfonate when concentration and exposure time are taken into account. Comparison of forward and reverse mutation assays in S. typhimurium reveals no important differences in sensitivities for the four compounds studied.
Animals↗
Toxicity and structure-activity relationships of cytochalasins.
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Animals↗
A prospective study of hprt mutant and mutation frequencies in treated cancer patients.
We previously reported that some Hodgkin's disease patients had elevated hprt mutant frequencies in peripheral blood lymphocytes long after cessation of therapy. To determine if these elevations in mutant frequency represent true persistently elevated mutation frequencies, we recruited for a prospective study six previously treated Hodgkin's disease patients and five patients who had been treated for squamous cell carcinoma of the head and neck. These individuals were studied several times over a 6-7-month period. The results confirmed that a subset of patients have persistently high mutant frequencies when compared to 71 previously studied controls. The present study was designed to determine if the elevated mutant frequencies of treated patients represented independent mutations or resulted from the in vivo expansion of single mutant cells. We used the polymerase chain reaction to examine DNA single-strand conformation polymorphisms at the T-cell receptor gamma locus of individual mutant clones. This analysis showed that at any given time 20.1% of the mutants from Hodgkin's disease patients and 17.5% of the mutants from squamous cell carcinoma patients consisted of siblings, identified as having identical polymerase chain reaction/single-stranded conformation polymorphism patterns. The remaining mutants had unique polymerase chain reaction/single-stranded conformation polymorphism patterns and therefore can be presumed to have arisen from independent mutational events. Particular sibling mutants generally did not persist over time. However, one patient had one mutant clone which persisted but slowly decreased in prevalence over a 7-month sampling period. The data demonstrate that treatments for cancer result in persistently elevated mutation frequencies at the hprt locus in some, but not all, patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Mutation assay in diploid human lymphoblasts: methodological aspects.
The protocol for a recently developed quantitative assay for mutation at the hgprt locus of human lymphoblasts is presented. Practical problems affecting ease of performance and reliability are discussed with the aim of making the assay available for assessment and possible use in other laboratories.
Cell Line↗