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 i.p.), chloroethylmethane sulfonate (CI-EMS, 35 or 50 mg/kg i.p.), and the Pharmacia & Upjohn
antitumor agents adozelesin (1.6, 4, 6, or 8 microg/kg i.v.) and
CC-1065 (6 microg/kg i.v.) were all negative in the
hprt mutation test. Results with
cyclophosphamide (CP, 75 mg/kg i.v.) were equivocal.
Adozelesin,
CC-1065, and CI-EMS treatments increased the percentage of T-lymphocytes with
chromosome aberrations, as well as inducing types of aberrations not seen in control cells. EMS and CP were not tested for
chromosome aberrations. We have previously shown that treatment of monkeys with 77 mg/kg ENU substantially increased the
hprt mutant frequency, with a lag time of approximately 77 days between treatment and peak MF values. The results of the present study suggest a low sensitivity of the
hprt mutation assay to certain classes of genotoxic agents in cynomolgus monkeys.