Diphtheria toxin resistance in human lymphocytes and lymphoblasts in the in vivo somatic cell mutation test

Journal Article · Tue Jan 01 04:00:00 EST 1985 · Environ. Mutagen.; (United States)

DOI:https://doi.org/10.1002/em.2860070603· OSTI ID:6181486

Tomkins, D J; Wei, L; Laurie, K E

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 (Dip/sup r/) 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 (TH-thymidine, autoradiography) or protein synthesis (TVS-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 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, Dip/sup r/ may not be a suitable marker for the somatic cell mutation test.

• Research Organization: McMaster Univ., Hamilton, Ontario
• OSTI ID: 6181486
• Journal Information: Environ. Mutagen.; (United States), Journal Name: Environ. Mutagen.; (United States) Vol. 7:6; ISSN ENMUD
• Country of Publication: United States
• Language: English

Related Subjects

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59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANTIGENS
AUTORADIOGRAPHY
AZINES
BACTERIAL DISEASES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MARKERS
BIOLOGICAL MATERIALS
BIOSYNTHESIS
BLOOD
BLOOD CELLS
BODY FLUIDS
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DIPHTHERIA
DISEASES
EVEN-ODD NUCLEI
FIBROBLASTS
HETEROCYCLIC COMPOUNDS
INFECTIOUS DISEASES
ISOTOPES
LABELLED COMPOUNDS
LEUKOCYTES
LIGHT NUCLEI
LYMPHOCYTES
MATERIALS
MUTATIONS
NUCLEI
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PROTEINS
PYRIMIDINES
RADIOISOTOPES
RIBOSIDES
SOMATIC CELLS
SOMATIC MUTATIONS
SULFUR 35
SULFUR ISOTOPES
SYNTHESIS
THYMIDINE
TOXIC MATERIALS
TOXINS
TRITIUM COMPOUNDS