A study of the frequency of sister-chromatid exchange and of thioguanine-resistant cells in mouse spleen lymphocytes after in vivo exposure to ethylnitrosourea.
As part of the development of a multi-endpoint, in vivo, mouse model for mutagenesis we have measured the frequency of sister-chromatid exchange (SCE) and the frequency of thioguanine-resistant (TGr) cells among the lymphocytes of the mouse spleen following acute, intraperitoneal exposure to ethylnitrosourea (ENU). The responses of these two endpoints have been monitored both as a function of the dose of ENU injected, ranging from 0 to 70 mg/kg, and as a function of time after injection, from 1 day to 72 days. The SCE frequency response was highest 1 day after the ENU was injected, increasing 2.5-fold over control values for mice that received 70 mg/kg, and declined to control values in all animals by 72 days. SCE showed a linear dose response both at 1 day and 8 days after injection. The frequency of TGr cells was at control levels at 1 day, but at 15, 36 and 72 days after ENU injection the frequency of TGr cells showed a linear dose response. In addition, the frequency of TGr cells increased linearly with time for both the 35 and 70 mg/kg doses. The frequency of TGr cells for mice that had received 70 mg ENU/kg 72 days previously, was 100-fold higher than in control animals, giving a frequency of 1.4 X 10(-4).
D000818:Animals; D004351:Drug Resistance; D005038:Ethylnitrosourea / Q000494:pharmacology*; D007700:Kinetics; D008214:Lymphocytes / Q000187:drug effects*; D051379:Mice; D009152:Mutagenicity Tests / Q000379:methods; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013154:Spleen / Q000187:drug effects; D013866:Thioguanine / Q000494:pharmacology*
D009607:Nitrosourea Compounds; D013866:Thioguanine; D005038:Ethylnitrosourea