Enumeration of 6-thioguanine-resistant T-lymphocytes in the peripheral blood of nonhuman primates (cynomolgus monkeys).
We have investigated the use of cynomolgus monkeys (Macaca fascicularis) as a model of somatic cell mutagenesis in non-human primates. Using techniques described by Albertini (Mutation Research 150:411-422, 1985) for similar studies in humans, the frequency of TG-resistant T-lymphocytes in the peripheral blood was determined in animals that were either untreated or treated with ethylnitrosourea. The frequency of TG-resistant cells in untreated males was (mean +/- SD) 6.0 +/- 5.9 per 10(6) cells and for untreated females was 2.9 +/- 2.7 per 10(6) cells. The spontaneous frequency of TG-resistant cells for all animals was 4.2 +/- 4.44 per 10(6) cells. Maximum frequency of TG-resistant cells for two animals treated with a single I.P. dose of ENU was 45.1 and 77.9 per 10(6) cells. Substantial increases in frequencies of TG-resistant cells were not seen until at least 63 days after treatment. The TG-resistant phenotype of clones isolated in the assay was stable after growth for 2 weeks in the absence of selective agent. Many of the TG-resistant clones selected were frozen for future molecular analysis.
Genetic Toxicology Unit, Upjohn Company, Kalamazoo, MI 49001.
D M
DM
Zimmer
C S
CS
Aaron
J P
JP
O'Neill
R J
RJ
Albertini
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002999:Clone Cells; D004351:Drug Resistance / Q000276:immunology; D005038:Ethylnitrosourea / Q000494:pharmacology*; D005260:Female; D008252:Macaca fascicularis; D008297:Male; D008957:Models, Genetic; D016296:Mutagenesis; D010641:Phenotype; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013866:Thioguanine / Q000494:pharmacology*
D013866:Thioguanine; D005038:Ethylnitrosourea