Cancer cell selectivity of 5-iodo-6-aminobenzopyrone (INH2BP) and methyl-3,5-diiodo-4(4 '-methoxyphenoxy) benzoate (DIME)

The cellular pharmacologic actions, as measured by cell killing, of INH2BP, DIME and INO(2)BA (+ BSO) were determined in three types of cancer cells a nd compared to their action on quiescent confluent human foreskin fibroblas t (HSF) and pre-confluent growing fibroblasts. The confluent HSF cells were completely refractory to the action of INH2BP and DIME, but were killed by INO(2)BA (+ BSO). Proliferating HSF and all three tumor cell types were ki lled by all three drugs. The apparent in vivo tumor specificity of INH2BP a nd DIME is explained by preferential cell cycle dependent selective drug up take: into tumor cells and by drug metabolism that reverses drug action in less vigorously cycling normal cells. The covalent binding of iodonitrosobe nzamide (formed from INO(2)BA) and its toxicity are regulated by the concen tration of GSH, and exhibit no cell cycle selectivity.