Induction of alkaline phosphatase in cultured human fibroblasts. Comparison of normal cells and those from patients with cystic fibrosis.

The membrane glycoprotein enzyme, alkaline phosphatase was induced in cultured human fibroblasts 
by dibutyryl cyclic AMP, sodium butyrate, the serum glycoprotein fetuin, the 
Tamm-Horsfall urinary glycoprotein, and by a number of inhibitors of DNA 
synthesis. The uninduced basal enzyme activity increased at later stages of 
growth when the cells became confluent. Induction by dibutyryl cyclic AMP 
or fetuin was most effective when the agents were added after 
the cells had reached stationary phase and was maximal after at 
least two days of exposure. The levels of induction resulting from 
the addition of pairs of the agents, dibutyryl cyclic AMP, n-butyrate 
and fetuin were additive indicating that these have different modes of 
action. The inhibitors of DNA synthesis, cytosine arabinoside, hydroxyurea, and methothrexate 
were less effective inducers. Bromodeoxyuridine which also has non-DNA mediated effects 
induced to the same extent as dibutyryl cyclic AMP. Similar experiments 
with sex- and age-matched cell strains derived from patients with cystic 
fibrosis failed to detect differences in the levels of induction from 
those observed in normal cells. In addition, the combined inductive effects 
of Tamm- Horsfall glycoprotein, isoproterenol and theophylline, were similar with normal 
and cystic fibrosis cells. 