Perturbation of cell kinetics on 9L rat brain tumor treated with BCNU, in vitro and in vivo (author's transl)

Abstract

Kinetic changes induced by 1, 3-bis(2-chloroethyl)-l-nitrosourea (BCNU) in 9L rat brain tumor were studied in vitro and in vivo by means of conventional autoradiography and flow cytometry (FCM). In vitro, 5 μg/ml BCNU, which resulted in 99% cell kill as measured by the colony forming efficiency assay, had the effects that most cells (more than 90%) were accumulated in G2 or M phase after one cell division, while cells in early G1 when BCNU had been given progressed to G2 and never divided. These effects were also revealed in vivo by using CD Fisher rats bearing 9L brain tumors treated with LD10 dose of BCNU which caused 99.9% cell kill. Accumulation of cells in G2 was also shown by flow cytometric study, but this time showed only 50% accumulation of cells at maximum 54 hrs after BCNU treatment. Rest of cells still remained in 2C peak of tumor even 78 hrs after treatment. Growth fraction of this tumor was 47-55%. This result suggests that these cells in 2C peak of tumor consisted of G0 cells. In summary, effects of BCNU on 9L rat brain tumor cells in vivo were well correlated with that in vitro so far as cycling cells were concerned. But it should be noticed that G0 cells could remain there even 78 hrs after BCNU treatment. These data also indicate that in vitro study was useful for estimation of the effects of BCNU treatment in vivo if the doses used for treatment in vivo could expect the same cell kill as that in vitro by colony forming efficiency assay. (Supported in part by CA-13525 and CA-19992 from NCI)