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 04:00:00 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), Journal Name: Environmental and Molecular Mutagenesis; (United States) Vol. 17:3; ISSN 0893-6692; ISSN EMMUE
• Country of Publication: United States
• Language: English

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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
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