The effect of time after treatment, treatment schedule and animal age on the frequency of 6-thioguanine-resistant T-lymphocytes induced in Fischer 344 rats by N-ethyl-N-nitrosourea.
The persistence of 6-thioguanine-resistant (TGr) T-lymphocytes was investigated in Fischer 344 rats treated with N-ethyl-N-nitrosourea (ENU) using two schedules. Male rats, aged 3 months, were given i.p. injections containing a total of 0, 50 or 100 mg ENU/kg either as a single treatment (single-dose group) or divided among 10 weekly treatments (split-dose group). At 1, 3, 5, 10, 20, 30 and 50 weeks after the single-dose treatment, and 10, 20, 30 and 50 weeks after beginning the split-dose regimen, animals were assayed for the frequency of TGr spleen lymphocytes. ENU produced significant dose- and time-dependent responses in the single- and the split-dose treatment groups. Although a few of the 50 mg/kg split-dose treatments were significantly higher than the comparative single-dose groups, the number of TGr lymphocytes produced by the two dosing regimens were generally similar. The frequency of TGr cells for control animals increased with the age of the animals. The mode of ENU administration did not greatly influence the percent cloning efficiency (%CE) of the non-selection cultures, although the %CE declined in animals over 10 months of age. To investigate the relationship between the frequency of TGr cells and the age of the animals at the time of ENU administration, additional rats aged 17 months were treated with a single dose of ENU and at 1, 5 and 10 weeks following exposure, the frequencies of TGr cells were determined from the isolated lymphocytes. No difference in mutagen sensitivity between rats treated at 3 months of age and those treated at 17 months of age was detected at the time points evaluated. The data demonstrate the persistence of ENU-induced TGr T-lymphocytes in the rat and suggest that the dose and possibly the treatment schedule, but not the age of the animal at the time of treatment, affect the response.
Aidoo
A
A
Department of Health and Human Services, Food and Drug Administration, Jefferson, AR.
Lyn-Cook
L E
LE
Heflich
R H
RH
George
E O
EO
Casciano
D A
DA
D000367:Age Factors; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004351:Drug Resistance; D005038:Ethylnitrosourea / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D016296:Mutagenesis / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D013601:T-Lymphocytes / Q000187:drug effects*; D013866:Thioguanine / Q000494:pharmacology; D013997:Time Factors
D013866:Thioguanine; D005038:Ethylnitrosourea