A guide for the performance of the Chinese hamster ovary cell/hypoxanthine-guanine phosphoribosyl transferase gene mutation assay.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
L L Yang
Publications and source records attributed to L L Yang.
Genotoxicity of fecapentaene-12 in bacterial and mammalian cell assay systems.
Fecapentaene-12 (Fec-12), a compound thought to be responsible for much of the mutagenicity in fecal extracts from groups at high risk for colon cancer, was assayed for genotoxic potential in a battery of bacterial and mammalian cell short-term assays. This compound demonstrated significant mutagenic activity with Salmonella typhimurium tester strains TA104, TA100 and TA98, inducing approximately 1400, 700 and 100 revertants/micrograms, respectively. Fec-12 caused dose-dependent increases in unscheduled DNA synthesis in both rat hepatocytes and human fibroblasts, indicating its potential genotoxicity to mammalian as well as bacterial cells. Finally, Fec-12 had the ability to induce neoplastic transformation in mouse BALB/c 3T3 cells in the absence of exogenous metabolic activation.
Animals↗
Depression in Chinese medical inpatients.
The authors studied depressive symptoms among 251 Chinese medical inpatients through the use of the Beck Depression Inventory. Assessment of 100 healthy Chinese volunteers validated the use of American score norms for Chinese subjects. A total of 47.8% of the 251 medical inpatients (N = 120) met the Beck scale criterion for depression. Beck scale scores varied with the occupation of patients and the severity of medical illness but did not vary with sex, age, marital status, duration of hospitalization, or medical diagnosis.
Adolescent↗
Mutations and homologous recombination induced in mammalian cells by metabolites of benzo[a]pyrene and 1-nitropyrene.
Metabolites of two structurally related chemical carcinogens, benzo[a]pyrene and 1-nitropyrene, were compared for their ability to cause cytotoxicity and induce mutations in normally repairing or nucleotide excision repair-deficient diploid human fibroblasts; for their ability to induce mutations in a defined gene sequence, supF, when a plasmid containing adducts formed by these carcinogens replicates in human 293 cells; and for their ability to induce homologous recombination between duplicated genes in mouse L cells. Both of the metabolites tested, i.e., (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha, epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) and 1-nitrosopyrene (1-NOP), form adducts on guanine. BPDE binds principally at the N2 position of guanine; 1-NOP binds to guanine at the C8 position. Results of the studies in diploid human cells indicated that when compared on the basis of equal numbers of DNA adducts, BPDE is more effective than 1-NOP in inducing mutations in DNA repair-proficient cells, but when compared in repair-deficient xeroderma pigmentosum human cells that do not remove such adducts from their DNA, the frequency of mutants induced per adduct is equal. These results suggest that during the time available for repair of potentially mutagenic lesions, repair-proficient human cells excise 1-NOP adducts more rapidly than they excise BPDE adducts. Molecular analysis of the specific kinds of mutations induced when a plasmid containing BPDE residues was allowed to replicate in human cells showed that BPDE induces mainly base substitution mutations, predominantly G:C to T:A transversions.(ABSTRACT TRUNCATED AT 250 WORDS)
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
Fecapentaene-12 causes DNA damage and mutations in human cells.
Fecapentaenes are mutagens found in human feces and may play a role in the pathogenesis of colon carcinoma. However, the genotoxic effects of fecapentaenes have not been previously studied in mammalian cells. We now report that fecapentaene-12 (fec-12), a prototype for these compounds, causes DNA single strand breaks, sister chromatid exchanges and mutations in cultured human fibroblasts. These results indicate that fec-12 is a potent genotoxic agent in human cells.
Cells, Cultured↗
Antihepatotoxic principles of Wedelia chinensis herbs.
Explore the source record for details and available documents.
Animals↗
Aldehyde-induced inhibition of DNA repair and potentiation of N-nitrosocompound-induced mutagenesis in cultured human cells.
Explore the source record for details and available documents.
Acetaldehyde↗
Genotoxicity of formaldehyde in cultured human bronchial fibroblasts.
Formaldehyde, a common environmental pollutant, inhibits repair of O6-methylguanine and potentiates the mutagenicity of an alkylating agent, N-methyl-N-nitrosourea, in normal human fibroblasts. Because formaldehyde alone also causes mutations in human cells, the compound may cause genotoxicity by a dual mechanism of directly damaging DNA and inhibiting repair of mutagenic and carcinogenic DNA lesions caused by other chemical and physical carcinogens.
Bronchi↗
Neuropsychological status of patients with congenital and rheumatic heart diseases: preoperative and postoperative comparison.
Thirty surgical patients receiving surgery for congenital heart or rheumatic heart disease were compared with a match control group on a battery of neuropsychological tests. Subjects were examined prior to surgery, 4 weeks post- and again 6 months postsurgery. Preoperative surgical subjects showed a generalized impairment in functioning suggestive of brain dysfunction secondary to hypoxia. Improvement following surgery was attributed to practice effects.
Adult↗
Xeroderma pigmentosum fibroblasts are more sensitive to asbestos fibers than are normal human fibroblasts.
Xeroderma pigmentosum fibroblasts (XPF) are defective in the repair of certain DNA adducts. We show here that XPF cells are more sensitive to the toxic effects of chrysotile, amosite and crocidolite asbestos than are normal human fibroblasts (NF). XPF cells from different complementation groups have a sensitivity to chrysotile which parallels the degree of their DNA repair deficiency. In addition, the survival of normal cells after chrysotile exposure increases with time if they are kept from replicating, while the survival of XPF cells under the same circumstances does not change.
Asbestos↗
Relationship between excision repair and the cytotoxic and mutagenic effect of the 'anti' 7,8-diol-9,10-epoxide of benzo[a]pyrene in human cells.
The cytotoxic and mutagenic effect of (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti BPDE) in normally excising diploid human cells treated just prior to onset of S was compared with that of cells allowed approximately 16 h for excision repair before onset of S and with that observed in excision-deficient xeroderma pigmentosum (XP12BE) cells. The cells were synchronized by release from density inhibition of cell replication. DNA synthesis began approximately 22 h after the cells were plated at lower density (i.e., 1.4 x 10(4) cells/cm2). The frequency of thioguanine-resistant mutants induced in normal cells treated just prior to onset of S was approximately 12- to 16-fold higher than that observed in cells treated in early G1 or treated in G0 (confluence) and then plated at lower density. The frequency approximated that expected for XP12BE cells from extrapolation of data obtained at lower doses. The frequency of mutants measured in normal cells treated in exponential growth was also much higher than that in the cells treated in early G1 or in G0. No such difference could be seen in XP12BE cells treated in exponential growth or in G0. In contrast to the mutagenicity data in the normal cells, there was no significant difference in the slope of the survival curve of normal cells treated at various times prior to S phase at low densities. However, normal cells treated even at the onset of S exhibited survival equal to XP12BE cells given a 4- to 5-fold lower dose. The data support the hypothesis that DNA synthesis is the cellular event which converts unexcised DNA lesions into mutations. However, they indicate that S is not the event primarily responsible for translating DNA damage into cell death. Accompanying studies on the rate of excision of anti BPDE adducts from the normal cells during the period prior to S support the conclusions.
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
Error-free excision of the cytotoxic,mutagenic N2-deoxyguanosine DNA adduct formed in human fibroblasts by (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene.
The ability of normal diploid human fibroblasts and excision repair-deficient xeroderma pigmentosum cells (XP12BE, complementation group A) to excise potentially cytotoxic or mutagenic lesions induced in DNA by (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BzaP-diol epoxide) was determined. Large populations of cells were prevented from replicating by being grown to confluence; after 3 days they were exposed to tritiated BzaP-diol epoxide for 2 hr. One set of cultures was immediately released and assayed for the number of residues covalently bound to DNA, percent survival of colony-forming ability, and frequency of induced mutations. After various periods of time in confluence, other sets were similarly released and assayed. The normal cells exhibited a gradual increase in survival with time held in confluence (recovery from potentially cytotoxic lesions) which was directly correlated with a gradual loss of radioactivity from their DNA and a gradual decrease in the frequency of induced mutations. In contrast, no loss of radioactively labeled carcinogen from the DNA of the XP12BE cells could be detected during a 6-day period and their percent survival and frequency of induced mutations did not change. DNA from normal cells harvested immediately after treatment or after 2, 4, or 8 days in confluence was enzymatically hydrolyzed and analyzed by high-pressure liquid chromatograhy. Only a single peak was detected that cochromatographed with a standard prepared from deoxyguanosine treated with BzaP-diol epoxide. The kinetics of decrease of tritium label in this specific peak corresponded to the decrease in radioactivity of the total DNA with time and with the kinetics of recovery of the cells from the potentially cytotoxic and mutagenic effects of BzaP-diol epoxide. These results suggest that the N2-deoxyguanosine adduct is responsible for these biological effects and indicate that excision repair of this lesion by the normal human cells is "error free."
Benzopyrenes↗
Purification and partial characterization of a procaryotic glycoprotein from the plasma membrane of Thermoplasma acidophilum.
The obligate, thermophilic, acidophilic mycoplasma, Thermoplasma acidophilum, grows optimally at 56 degrees C and pH 2.0. Its plasma membrane possessed 21--22 protein bands that were resolved by polyacrylamide gel electrophoresis. One major membrane protein, molecular weight 152 000, which stained for carbohydrate with periodic acid-Schiff reagent, accounted for 32% (w/w) of the total membrane proteins. It was isolated and further purified by concanavalin A affinity chromatography. The carbohydrate content amounted to less than 10% (w/w) compared to that of the entire glycoprotein. The carbohydrate moiety consisted mainly of mannose residues with branched alpha 1 leads to 2 linkages at the non-reducing ends of the glycopeptide as determined by permethylation followed by gas chromatography-mass spectrometry analysis. The reducing end was an N-glycosidic linkage between asparagine and N-acetylglucosamine. The amino acid composition of this glycoprotein showed 62 mol% hydrophobic residues, while the acidic amino acid content contributed 9 mol% more than that of the basic amino acids. The existence of membrane glycoproteins in the procaryotic, wall-less T. acidophilum may provide a protective coat for the plasma membrane. The stereochemistry and the conformation of the carbohydrate chains, in conjunciton with water turgor, may contribute to the rigidity of the membrane and the cation binding.
Adaptation, Biological↗
Structure of membrane lipids and physico-biochemical properties of the plasma membrane from Thermoplasma acidophilum, adapted to growth at 37 degrees C.
Thermoplasma acidophilum, a mycoplasma-like organism, grows optimally at 56 degrees C and pH2. The low temperature extreme of growth is 37 degrees C. The plasma membrane of cells grown at 37 degrees C was isolated and characterized physicobiochemically. Membrane lipids which comprise 25% of the membrane dry weight consist mainly of two repetitively methyl-branched C40 side chains that were ether-linked to two glycerol molecules. The lipid structures were elucidated by combined gas chromatography-mass spectroscopy, direct probe mass spectroscopy and 13C NMR. 37 degrees C-grown cells contained lipids with 42% more pentane cyclization than the 56 degrees C-grown cells. In 37 degrees C-grown cells, phospholipid and serine content decreased by about 10% each, carbohydrate content increased by 5%. EPR studies demonstrated an increase in membrane lipid fluidity of 37 degrees C-grown cells with an upper transition temperature at 35 degrees C which was shifted down by 10 degrees C compared with cells grown at 56 degrees C. Membrane-bound ATPase activities also indicated similar changes upon adaptation. There is a close correlation between membrane fluidity and physiological functioning of this membrane-bound enzyme.
Adenosine Triphosphate↗
[Soft tissue injuries].
Explore the source record for details and available documents.
Wounds and Injuries↗
[Myasthenia gravis and its nursing care].
Explore the source record for details and available documents.
Myasthenia Gravis↗
Mutagenesis of xeroderma pigmentosum fibroblasts by acrolein.
Acrolein, a short-chain aldehyde encountered as a component of tobacco smoke and as a ubiquitous environmental contaminant, was tested for its toxic and mutagenic effects toward human fibroblast cells. We found that human cells characterized by a deficiency in DNA repair (cells from xeroderma pigmentosum (XP) patients) were much more sensitive (D37 approximately equal to 0.25 microM) to the cytotoxic effects of acrolein than were cells from normal individuals (D37 approximately equal to 0.8 microM). Acrolein was also strongly mutagenic to the XP cells (a dose response was observed between 0.2 and 0.8 microM acrolein); however acrolein did not induce an increase in the mutant frequency of normal fibroblasts. Possible reasons for this apparent lack of mutagenicity in normal human cells are discussed.
Acrolein↗
Antihepatotoxic actions of Formosan plant drugs.
One hundred twenty-nine samples of Formosan plants were screened for antihepatotoxic activity in primary cultured hepatocytes to reveal that 19 and 26 plants exhibited more than 50% inhibition against cytotoxicity produced by carbon tetrachloride and D-galactosamine, respectively. Plants which disclosed significant antihepatotoxic activity in both assay methods are: Wedelia chinense, Mallotus repandus, Phyllantus urinaria, Loranthus parasiticus, Ludwigia octovalvis, Onychium japonicum, Tamarix chinensis and Ampelopsis brevipedunculata.
Animals↗