A RETINOIC ACID-RESISTANT HL-60 CELL CLONE SENSITIVE TO N-(4-HYDROXYPHENYL) RETINAMIDE-MEDIATED CLONAL GROWTH-INHIBITION

Among the Retinoic Acid (RA) derivatives, retinamides, and in particul ar N-(4-hydroxyphenyl) retinamide (4-HPR), are currently being investi gated in selected cases of cancer chemoprevention. The cellular target range, however, seems to be limited, as cells of hemopoietic origin a re virtually incapable of terminal differentiation upon addition of th e compound. We have reconsidered the effect of 4-HPR on HL-60 cells by taking advantage of a mutant clone, generated in our laboratory, unre sponsive to RA but highly responsive to dimethylsulfoxide (DMSO). We s how here that this clone, upon addition of 4-HPR, although unable of u ndergoing full differentiation, shows considerable reduction of clonal growth. Moreover, the combination of 4-HPR and RA resulted in a much greater effect than the administration of 4-HPR alone. We suggest that 4-HPR and RA, at least in terms of mediating growth inhibition, may f ollow different metabolic pathways.