[Animal Modeling]-Optimization of the dose-effect relationship between N-ethyl-N-nitrosourea and cyclophosphamide in the Pig-a gene mutation test in rats

  OBJECTIVE: To study the effect of different doses of N-ethyl-N-nitrosourea (ENU) and cyclophosphamide (CP) on the removal rate of ankyrin CD59 on the peripheral red blood cells of SD rats, and carry out Pig-a gene mutation test.

  Method: SD rats were randomly divided into 4 groups based on body weight and peripheral blood RBCCD59. That is, the vehicle control group, the CP 40 mg/kg administration group, the ENU 10 mg/kg administration group, and the ENU 40 mg/kg administration group were respectively injected into the vehicle control group by intraperitoneal exposure. Before exposure and 7, 14, 21, 28, 42 and 56 days after exposure, they were weighed and exsanguinated, and the incidence of RBCCD59 in peripheral blood was detected by flow cytometry.

  Result: The body weight and weight gain of the ENU10mg/kg and ENU40mg/kg groups were not significantly different compared with the vehicle control group. At each time point, the body weight and weight gain dose of CP40mg/kg group decreased (P \u003c0.05)? 28 to 42 days after administration, CP40mg/kg administration group, 56 days after administration, ENU10mg/kg administration group, 42 days and 56 days after administration, ENU40mg/kg administration group, RBCCD59-peripheral blood There was a dose-response relationship from 7 to 14 days, increasing from the 21st, 21st day to 28, 42 and 56 days (P\u003c0.05).

  Conclusion: In the Pig-a gene mutation test, ENU enhanced the incidence of RBCCD59- in the peripheral blood of rats, which was better than CP. The dose of 40 mg/kg was better than that of 10 mg/kg. The test cycle was 28 days.