The pathophysiology of neurofibromatosis. I. Resistance in vitro to 3-nitrotyrosine as an expression of the mutation.
The in vitro expression of the autosomal dominant mutation responsible for neurofibromatosis was probed using the amino acid analogue 3-nitrotyrosine as a cell culture selective agent. The presence of 3-nitrotyrosine in culture medium led to inhibition of growth and cell death among normal skin fibroblasts in log phase growth, whereas cell strains derived from six different patients' neurofibromas or skin cells, or both, exhibited a consistently enhanced ability to survive under the same conditions. At 0.8 mM 3-nitrotyrosine, four patient-derived skin fibroblast strains could be differentiated from five strains of control skin fibroblasts with a high level of confidence (P < 0.0000). In the same way four neurofibroma-derived fibroblast strains were differentiated from control skin fibroblasts (P < 0.0022). Neurofibroma-derived cells were not different from control cells when treated with 5-fluorotryptophan or p-fluorophenylalanine.