Induction of 6-thioguanine-resistant lymphocytes in Fischer 344 rats following in vivo exposure to N-ethyl-N-nitrosourea and cyclophosphamide

Journal Article · Tue Jan 01 00:00:00 EST 1991 · Environmental and Molecular Mutagenesis; (United States)

DOI:https://doi.org/10.1002/em.2850170302· OSTI ID:6051410

Aidoo, A; Lyn-Cook, L E; Mittelstaedt, R A; Heflich, R H; Casciano, D A ^[1]

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1. Food and Drug Administration, Jefferson, AR (United States)

The authors have developed a limiting dilution clonal assay for determining the frequency of 6-thioguanine-resistant (TG{sup r}) lymphocytes produced in rats by in vivo exposure to genotoxic agents. Lymphocyte cloning efficiencies (CEs) were highest in plates containing both irradiated TK6 cells and irradiated autologous feeder cells. To measure the effects of chemical mutagens on the frequency of TG{sup r} lymphocytes, rats were given a single i.p. injection of N-ethyl-N-nitrosourea (ENU), a direct-acting alkylating agent, cyclophosphamide (CP), an indirect acting alkylating agent. Lymphocytes were isolated, primed, and cloned at 4 weeks after CP treatment and at 1,2,4 and 6 weeks after ENU treatment. CE in these cultures ranged from 12% to 27%. Cultures were also established for measuring CE in the presence of 6-thioguanine (TG). The dose-dependent responses obtained with both ENU and CP treatments suggest that rat lymphocytes are sensitive to direct- and indirect-acting alkylating agents administered in vivo and that the rat lymphocyte assay is a useful complement to the in vivo/in vitro mouse assay for determining the mutagenicity of environmental toxicants.

• OSTI ID: 6051410
• Journal Information: Environmental and Molecular Mutagenesis; (United States), Vol. 17:3; ISSN 0893-6692
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKYLATING AGENTS
BIOLOGICAL EFFECTS
LYMPHOCYTES
BIOLOGICAL RADIATION EFFECTS
CESIUM 137
DOSE-RESPONSE RELATIONSHIPS
GAMMA RADIATION
GUANINE
NITROSOUREAS
RATS
ALKALI METAL ISOTOPES
AMINES
ANIMAL CELLS
ANIMALS
AROMATICS
AZAARENES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CESIUM ISOTOPES
CONNECTIVE TISSUE CELLS
ELECTROMAGNETIC RADIATION
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
IONIZING RADIATIONS
ISOTOPES
LEUKOCYTES
MAMMALS
MATERIALS
NITROSO COMPOUNDS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PURINES
RADIATION EFFECTS
RADIATIONS
RADIOISOTOPES
RODENTS
SOMATIC CELLS
VERTEBRATES
YEARS LIVING RADIOISOTOPES
560300* - Chemicals Metabolism & Toxicology
560120 - Radiation Effects on Biochemicals
Cells
& Tissue Culture