Hematoporphyrin (HP) derivatives have been recognized chiefly as growth inhibitors of neoplastic tissues within the context of tumor phototherapy. We investigated the possibility that HP may also modify the growth potential of rapidly growing nonneoplastic tissues and describe the effect of HP on the metabolism and growth of embryonic chick cartilage in vitro. In the embryonic chick pelvic rudiment prolonged organ-culture bioassay, pelvic rudiment growth was significantly inhibited when HP 0.01 mmol/L was added to the culture medium (after 5 days in organ culture, weight increment in presence of serum + 136% +/- 12% v + 90% +/- 8% in presence of serum plus HP 0.01 mmol/L and + 43% +/- 10% in presence of serum plus HP 0.025 mmol/L, P less than .001). Inhibition of cartilage growth was irreversible if HP was added to the culture medium without serum for 2 days, but partial reversibility was observed when hypophysectomized rat serum was present during that period. Therefore, the protective effect of serum was apparently unrelated to pituitary-dependent growth factors. Binding of HP to albumin did not eliminate its inhibitory effects. Uridine incorporation into RNA and, to a lesser extent, sulfate incorporation into proteoglycans were reduced in cartilage incubated overnight with HP. Our study shows that HP can exert partially reversible inhibition of cartilage metabolism and growth suggesting potentially novel tissue actions for this compound.
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http://dx.doi.org/10.1016/0026-0495(90)90053-f | DOI Listing |
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