Inhibition of iodinated nerve growth factor binding by the suspected tumor promoters saccharin and cyclamate.

The strong correlation between tumor-promoting activity and the capacity to inhibit nerve growth factor-induced neurite outgrowth for a number of compounds prompted studies on the suspected bladder tumor promoters saccharin and cyclamate. These artificial sweeteners reversibly inhibited neurite outgrowth and binding of [125I]nerve growth factor in embryonic chick sensory ganglia cells. Curves showing the dose-dependent inhibition of response and the dose-dependent inhibition of binding to high affinity sites were closely parallel. The inhibition appeared to be due to a reduction in the affinity rather than to a change in the number of binding sites, as indicated by the extent of reduction in the association rate. These results suggest that alteration of cellular differentiation by tumor promoters may result from interactions with receptor systems that regulate specialized cell functions.