This study was performed to define the biologically active growth modu
lators in human gastric juice. Mitogenic activity was evaluated by the
incorporation of [H-3]thymidine into 3T3 fibroblasts. A negative corr
elation was observed between pH and mitogenic activity in gastric juic
e (r = -0.45, P < 0.01). The concentrations of epidermal growth factor
(EGF), transforming growth factor-alpha and -beta(1) (TGF-alpha and -
beta(1)), platelet-derived growth factor (PDGF), and basic fibroblast
growth factor (bFGF) in gastric juice did not explain these changes in
mitogenic activity. Gel filtration identified growth;-stimulating act
ivity due to small molecule mitogens (less than 13 kDa), and growth in
hibitory activity only in neutral samples due to a macromolecular subs
tance (larger than 240 kDa) susceptible to trypsin digestion and heat
and acid treatments. We conclude that acidity-dependent changes in mit
ogenic activity observed in this study are due to appearance of acid-u
nstable, high-molecular-weight, growth-inhibitory substance.