Lack of response to multiple genotoxic agents at the hprt locus in peripheral blood T‐lymphocytes of cynomolgus monkeys

  title={Lack of response to multiple genotoxic agents at the hprt locus in peripheral blood T‐lymphocytes of cynomolgus monkeys},
  author={David M. Zimmer and Philip R. Harbach and S S Mattano and R L Yu and W. B. Mattes and C. S. Aaron},
  journal={Environmental and Molecular Mutagenesis},
We tested the ability of a series of known genotoxic agents to cause mutations at the hprt locus in peripheral blood T‐lymphocytes of cynomolgus monkeys as measured by the ability to form clones in the presence of 6‐thioguanine. Ethylmethane sulfonate (EMS, 300 mg/kg IP), chloroethylmethane sulfonate (Cl‐EMS, 35 or 50 mg/kg IP), and the Pharmacia & Upjohn antitumor agents adozelesin (1.6, 4, 6, or 8 μg/kg IV) and CC‐1065 (6 μg/kg IV) were all negative in the hprt mutation test. Results with… 
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Enumeration of 6‐thioguanine‐resistant T‐lymphocytes in the peripheral blood of nonhuman primates (cynomolgus monkeys)
The TG‐resistant phenotype of clones isolated in the assay was stable after growth for 2 weeks in the absence of selective agent, and many of the TG‐ resistant clones selected were frozen for future molecular analysis.
DNA sequence analysis of spontaneous and n‐ethyl‐n‐nitrosourea‐lnduced hprt mutations arising in vivo in cynomolgus monkey t‐lymphocytes
This is the first report of the sequence of the coding region of the cynomolgus monkey hprt gene and PCR/DNA sequence analysis of seven spontaneous mutant T‐cell clones, as well as 23 mutant clones isolated 63 and 601 days after treatment with ethylnitrosourea.
Induction of 6‐thioguanine‐resistant lymphocytes in fischer 344 rats following in vivo exposure to n‐ethyl‐n‐nitrosourea and cyclophosphamide
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.
In vivo mutagenesis in the cynomolgus monkey: Time course of HPRT mutant frequency at long time points following ethylnitrosourea exposure
In four animals treated with a single intraperitoneal dose of 77 mg/kg ethylnitrosourea, mutant frequency increased with time, peaking 70 to 100 days after treatment and declining to a plateau that was higher than the predose mutant frequency in both animals.
Factors that affect the frequency of thioguanine-resistant lymphocytes in mice following exposure to ethylnitrosourea.
The frequency of thioguanine(TG)-resistant lymphocytes in mice treated with ethylnitrosourea (ENU) was followed and one set of control mice was found to have a 10-fold elevated frequency of TG-resistant cells in both the spleen and thymus, indicating that mutations can occur in stem cells of untreated animals.
Southern blot analysis of T‐cell receptor gene rearrangements in cynomolgus monkeys, and identification of a progenitor cell HPRT mutation
The use of probes for human TCR B and y genes to characterize TCR rearrangements in cynomolgus monkeys is reported and a preliminary in vivo mutation study, the animal was treated with the investigational potent mutagen and antitumor agent adozelesin and no increase in HPRT mutant frequency was observed.
Differential mutant quantitation at the mouse lymphoma tk and CHO hgprt loci.
It is significant that the four acrylates evaluated give little or no evidence of genotoxicity when evaluated using selection for HGPRT-deficient mutants, yet are clearly clastogenic to the same cells in the same experiment.