Enhancement by tocoretinate of epidermal growth factor-induced DNA synthesis in human intestinal epithelial cells.

Tocoretinate (TR) is a hybrid compound composed of alpha-tocopherol esterified with retinoic acid. The present study was conducted to clarify whether or not TR affects DNA synthesis in a human intestinal cell line, FHs 74 Int. In these cells, addition of 10% serum resulted in an approximately 10-fold increase in DNA synthesis as assessed by [3H]thymidine incorporation. Epidermal growth factor (EGF) augmented DNA synthesis three- to fourfold. When EGF was added together with insulin-like growth factor-I (IGF-I), which had only a small effect by itself, a combination of these growth factors reproduced the effect of serum. In quiescent FHs 74 Int cells, TR had no effect on DNA synthesis by itself. However, when quiescent cells were pretreated with TR for 24 hr, DNA synthesis induced by EGF was markedly enhanced. Thus, in TR-pretreated cells, EGF stimulated DNA synthesis to the same extent as 10% serum. The effect of TR was dose-dependent and the maximal effect was obtained by 10(-7) M TR. Pretreatment with TR enhanced the effect of EGF on DNA synthesis but did not change the dose-response relationship for EGF-mediated DNA synthesis. All-trans-retinoic acid had similar stimulatory effect on EGF-induced DNA synthesis. When the medium was changed during the treatment with TR, the effect of TR on DNA synthesis was reduced. In addition, pretreatment with TR resulted in release of immunoreactive IGF-I into medium. Finally, the effect of TR was attenuated by an addition of antibody against IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)