Effect of Podophyllin on Tumor Cells in Tissue Culture.

Abstract

Podo-phyllin exerts a selectively damaging effect on mouse tumor cells in tissue culture over the concn. range 0.08-20.0 mg./l. Within this concn. range, roller tube explants from the in-strain transplantable mouse tumors L946 (sarcoma from C-57 mice) and MA387 (lung tumor from AK mice) were drastically damaged, whereas similar explants of normal fetal mouse skin were virtually undamaged. Damage to growing cells was manifest within 24 hrs. by loss of cytoplasmic processes, cell rounding, heavy cytoplasmic granulation, inhibition of cell migration, fragmentation of the nuclear chromatin, and pyknosis. These damaging effects are easily reversible in normal cells by the removal of the podophyllin within 24 hrs. after application, but are much less reversible in tumor cells. Podophyllotoxin is not as effective as podophyllin in causing selective damage in vitro. For purposes of comparison, a method of expressing cell damage in numerical form was devised. The resulting Selective Index of damage is useful in comparing the selectively damaging effects of different compounds. In vivo studies with mice bearing tumors L946 and MA387 confirm the selective tumor damaging effects of podophyllin first obtained in tissue culture.