RETINOID METABOLISM AND ALL-TRANS-RETINOIC ACID-INDUCED GROWTH-INHIBITION IN HEAD AND NECK SQUAMOUS-CELL CARCINOMA CELL-LINES

Retinoids can reverse potentially premalignant lesions and prevent sec ond primary tumours in patients with head and neck squamous cell carci noma (HNSCC). Furthermore, it has been reported that acquired resistan ce to all-trans retinoic acid (RA) in leukaemia is associated with dec reased plasma peak levels, probably the result of enhanced retinoid me tabolism, The aim of this study was to investigate the metabolism of r etinoids and relate this to growth inhibition in HNSCC. Three HNSCC ce ll lines were selected on the basis of a large variation in the all-tr ans RA-induced growth inhibition. Cells were exposed to 9.5 nM (radioa ctive) for 4 and 24 h, and to I and 10 mu M (nonradioactive) all-trans RA for 4, 24, 48 and 72 h, and medium and cells were analysed for ret inoid metabolites. At all concentrations studied, the amount of growth inhibition was proportional to the extent at which all-trans-, 13- an d g-cis RA disappeared from the medium as well as from the cells, This turnover process coincided with the formation of a group of as yet un identified polar retinoid metabolites. The level of mRNA of cellular R A-binding protein II (CRABP-II), involved in retinoid homeostasis, was inversely proportional to growth inhibition, These findings indicate that for HNSCC retinoid metabolism may be associated with growth inhib ition.