N-methylformamide-mediated enhancement of in vitro tumor cell chemosensitivity.

The effects of the differentiation-inducing polar solvent N-methylformamide (NMF) on the in vitro response of murine hepatocarcinoma (HCa-1) cells to 1,3-bis(2-chloroethyl)-1-nitrosourea, cis-diamminedichloroplatinum (II), and melphalan were investigated using the sister chromatid exchange (SCE) and cell survival assays. When cells were exposed to 1.25% NMF, cell culture doubling time increased from 12 to 43 h and cell volume increased from 940 microns 3 to 1440 microns 3. Growth of HCa-1 cells in NMF for 96 h before drug treatment enhanced the SCEs induced by each of the three chemotherapeutic agents. For each drug, maximum enhancement occurred after 72 h of NMF pretreatment, and the enhancement was eliminated 48 h after NMF was removed. Pretreatment with 1.25% NMF for 96 h also enhanced the cell kill induced by each drug. NMF exposure modified primarily the low-dose shoulder region of each drug cell survival curve. The data indicate that NMF is an effective chemosensitizing agent for HCa-1 cells in vitro and suggest that NMF may provide clinical benefits when administered in combination with antineoplastic drugs.