In vitro and in vivo studies of the antileukemic action of n,n'-bos [p-(n'-methylamidino)phenyl]terephthalamidine, tetrahydrochloride (NSC 57155) on P815 leukemic cells.

The effect of various concentrations of N,N″ -bis[ p -( N′ -methylamidino)phenyl]terephthalamidine, tetrahydrochloride (NSC 57155)[4][1] for various incubation periods on P815Y cells in tissue culture and on sensitive P815 and resistant P815/NSC 57155 cells in mice was studied. A 50% growth inhibition in tissue culture after 72 hr was produced by incubation with 300 µg/ml for 15–30 min, 100 µg/ml for 1–2 hr, or 1 µg/ml for 72 hr. The incorporation of NSC 57155-14C into cells and its distribution in nuclei and cytoplasm were studied with a 2-hr incubation at a concentration of 100 µg/ml. After that period most of the activity was found in the cytoplasm and only very little in the cell nuclei. More than 50% of this activity could be extracted with nonpolar solvents. Incorporation of NSC 57155-14C occurred at a slower rate in resistant P815/NSC 57155 cells than in sensitive P815 cells. When P815 and P815/NSC 57155 cells were bioassayed after in vitro incubation with 100 µg/ml of NSC 57155, the cytostatic effect was found to be time dependent. P815/NSC 57155 cells were somewhat sensitive to these high concentrations of the drug, but a longer incubation period was required than with the sensitive cells. [1]: #fn-4