CINEMICROGRAPHIC DETERMINATION OF CELL PROGRESSION AND DIVISION ABNORMALITIES AFTER TREATMENT WITH 1, 3 BIS(2-CHLOROETHYL)-1-NITROSOUREA

Time-lapse photography was used to study cell-cycle progression and cell-division abnormalities in rat 9L brain tumor cells after treatment in culture with 2 μg/ml and 5 μg/ml of 1, 3 bis(2-chloroethyl)-1-nitrosourea (BCNU). Cells treated in G1 were extensively delayed in reaching the first mitosis after treatment, whereas cells treated in S and G2 were not. However, cells treated in G1 returned to nearly normal generation times in the first full post-treatment generation, whereas cells treated in S and G2 had an abnormally long generation time in that generation. Most cells completed or at least attempted on or two divisions before dying, therby producing a 3- to 4-fold increase in cell number before any decrease was evident. Both the length of time required for cells to die and the number of divisions made before the cells died depended on the BCNU concentration to which they were exposed. Nearly all cells underwent abnormal divisions before dying, including tripolar divisions, unsuccessful divisions, divisions with the loss of a non-viable cytoplasmic mass, and unorganized divisions. The length of time that cells remained rounded at division depended on both the BCNU concentration and the generation after treatment. BCNU induced chromosomal aberrations that could be responsible for killing the cells or for the observed division delays and abnormalities. © 1979.