Document Detail


Diphtheria toxin resistance in human lymphocytes and lymphoblasts in the in vivo somatic cell mutation test.
MedLine Citation:
PMID:  4065058     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
It has been shown that circulating peripheral blood lymphocytes can be used for the enumeration of 6-thioguanine-resistant cells that presumably arise by mutation in vivo. This somatic cell mutation test has been studied in lymphocytes from human populations exposed to known mutagens and/or carcinogens. The sensitivity of the test could be further enhanced by including other gene markers, since there is evidence for locus-specific differences in response to mutagens. Resistance to diphtheria toxin (Dipr) seemed like a potential marker to incorporate into the test because the mutation acts codominantly, can readily be selected in human diploid fibroblasts and Chinese hamster cells with no evidence for cell density or cross-feeding effects, and can be assayed for in nondividing cells by measuring protein synthesis inhibition. Blood samples were collected from seven individuals, and fresh, cryopreserved, or Epstein-Barr virus (EBV)-transformed lymphocytes were tested for continued DNA synthesis (3H-thymidine, autoradiography) or protein synthesis (35S-methionine, scintillation counting). Both fresh and cryopreserved lymphocytes, stimulated to divide with phytohemagglutinin (PHA), continued to synthesize DNA in the presence of high doses of diphtheria toxin (DT). Similarly, both dividing (PHA-stimulated) and nondividing fresh lymphocytes carried on significant levels of protein synthesis even 68 hr after exposure to 100 flocculating units (LF)/ml DT. The findings were confirmed in cord blood lymphocytes, ruling out the possibility that diphtheria immunization could have led to a selection of Dipr lymphocytes. One lymphoblast line (EBV-transformed lymphocytes) showed a reduction in protein synthesis to 0.2% of controls only at 192 hr after exposure to 100 LF/ml. The results suggest that human T and B lymphocytes may not be as sensitive to DT protein synthesis inhibition as human fibroblast and Chinese hamster cells. For this reason, Dipr may not be a suitable marker for the somatic cell mutation test.
Authors:
D J Tomkins; L Wei; K E Laurie
Related Documents :
2826058 - Epstein-barr virus transformed b cell lines derived from patients with systemic lupus e...
15876358 - Elevated expression of cd30 in adult t-cell leukemia cell lines: possible role in const...
3039258 - Phenotypic, cytogenetic and molecular characterization of a new b-chronic lymphocytic l...
8525808 - In situ polymerase chain reaction detection of htlv-i provirus and expression of the p5...
15563588 - Processing of notch and amyloid precursor protein by gamma-secretase is spatially disti...
14594508 - Large-scale immunomagnetic selection of cd14+ monocytes to generate dendritic cells for...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Environmental mutagenesis     Volume:  7     ISSN:  0192-2521     ISO Abbreviation:  Environ Mutagen     Publication Date:  1985  
Date Detail:
Created Date:  1986-01-07     Completed Date:  1986-01-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7909737     Medline TA:  Environ Mutagen     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  811-20     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Cells, Cultured
DNA / biosynthesis
Diphtheria Toxin / toxicity*
Drug Resistance
Humans
Hypoxanthine Phosphoribosyltransferase / genetics
Lymphocytes / drug effects*
Mutagenicity Tests / methods*
Protein Biosynthesis
Thioguanine / pharmacology
Chemical
Reg. No./Substance:
0/Diphtheria Toxin; 154-42-7/Thioguanine; 9007-49-2/DNA; EC 2.4.2.8/Hypoxanthine Phosphoribosyltransferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Lipidosis of pulmonary macrophages in the dystrophic hamster.
Next Document:  Induction of micronuclei in maize root-tip cells and a correlation with forward mutation at the yg2 ...