In vivo mutagenesis in the cynomolgus monkey: time course of HPRT mutant frequency at long time points following ethylnitrosourea exposure.
We have monitored mutant frequency at the HPRT locus in peripheral blood lymphocytes of cynomolgus monkeys using a clonal assay in which mutants are selected by resistance to 6-thioguanine. Among untreated animals, the mean spontaneous mutant frequency was 2.9 +/- 2.9 x 10(-6) (standard deviation, based on 131 determinations in 33 animals), in good agreement with HPRT mutant frequencies in other species. 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. Mutant frequency in two of the four animals was monitored at intervals for 6 years, and a second identical treatment was given about 830 days after the first. Mutant frequency again peaked in these two animals 70 days after the second dose and decreased following peak values, declining to a plateau that was higher than the predose mutant frequency in both animals. This pattern was repeated following the second ethylnitrosourea treatment. Fractionating the dose of ethylnitrosourea into five equal daily injections had no effect on mutant frequency in two animals when compared to a single dose.
Zimmer
D M
DM
Pharmacia & Upjohn, Inc., Kalamazoo, Michigan 49007, USA.
Aaron
C S
CS
D000818:Animals; D005038:Ethylnitrosourea / Q000633:toxicity*; D005787:Gene Frequency; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008214:Lymphocytes / Q000187:drug effects*; D008252:Macaca fascicularis / Q000235:genetics*; D016296:Mutagenesis / Q000187:drug effects*; D009153:Mutagens / Q000633:toxicity*; D013997:Time Factors
D009153:Mutagens; D007041:Hypoxanthine Phosphoribosyltransferase; D005038:Ethylnitrosourea