GROWTH PROMOTION BY HOMOCYSTEINE BUT NOT BY HOMOCYSTEIC ACID - A ROLEFOR EXCESSIVE GROWTH IN HOMOCYSTINURIA OR PROLIFERATION IN HYPERHOMOCYSTEINEMIA

Excessive growth of long bones in patients with homocystinuria is stil l unexplained and previous work incriminating homocysteic acid could n ot be confirmed by others. In vitro studies from our laboratory showed that homocysteine stimulated growth in a clonogenic assay. This obser vation made us study plasma cyclin dependent kinase (CDK), homocyst(e) ine and homocysteic acid in 10 patients with homocystinuria and 20 con trols. In addition, homocysteine and homocysteic acid were tested in a clonogenic assay to correlate the growth promoting activity with CDK. Plasma CDK (protein) correlated strongly with homocysteine (r = 0.84) but not with homocysteic acid. Supernatants of the clonogenic assay s amples showed up to three times higher CDK levels in the presence of h omocyst(e)ine but not homocysteic acid. In vitro data and the strong c orrelation between homocysteine and CDK suggest a role for homocystein e stimulating CDK, the starter of mitosis, with subsequent stimulation of growth. (C) 1998 Elsevier Science B.V. All rights reserved.