Rat glial tumors, induced by injections of N-nitrosomethylurea, were plated and propagated in culture. Among a few cell strains obtained, one clone contains S-100 protein, which is unique to brain in vertebrates. Stationary-phase cultures contain approximately ten times more S-100 protein per cell than exponentially growing cells. When injected into newborn rats, cells producing S-100 grew as a glial tumor, which contained S-100 protein.

✓ Rat glial tumors, induced by weekly injections of N-nitrosomethylurea for 8 months, were plated and propagated in culture. Cells grew as a glial tumor when injected back into various sites in newborn rats, and were then carried for many generations by transplantations from rat to rat or by alternate culture and animal passage. Light, phase, and electron microscopy of the cultured cells showed great variability among the glial types in all the primary tumors, in the cultures grown from them, and in the secondary in vivo tumors grown from the cultures. Many unmistakable stigmata of glia were conserved. Cloned cultures (derived from a single cell) were frozen and stored, and upon thawing resumed growth with their original histological appearance. Tumor lines from these cultured cloned strains showed much more constant growth rates and cell types; two stable lines were carried for many generations: a slow-growing astrocytoma and a faster growing glioblastoma. The distinctive neural protein called “S-100” was detected in soluble extracts of cultured cells from all five different primary tumors studied and the secondary tumors grown from them. It represented 0.2% to 0.4% of the soluble proteins extracted from the cultures, and was also present in some clonal strains and their derived tumors. One clonal strain after a few hundred generations continues to synthesize S-100. It is concluded that clonally derived cultures of gliomas histologically similar to those in man provide a stable and suitable model in rats for the study of human glia and gliomas.

—The relationships between plasma tryptophan and 5‐HT metabolism in the CNS were studied in newborn rats and compared with adults. Both the concentration of free tryptophan in plasma and that of the amino‐acid in brain were much higher immediately after birth than later on. Drugs such as salicylate and chlordiazepoxide, which increased brain tryptophan concentrations in adults by displacing the plasma amino acid bound to serum albumin, were ineffective in newborn rats: most of the amino acid being already free in their plasma. The study of 5‐HT metabolism in brain stem slices revealed that the affinity of the uptake process for tryptophan was higher in newborn than in adult animals, whereas the reverse situation was observed for the enzyme complex involved in 5‐HT synthesis (lower apparent Km in adults). In addition, the catabolism of newly synthesized 5‐HT was more rapid in newborn than in adult tissues. Finally, the free state of tryptophan in plasma of newborn animals induced in brain both a high amino acid concentration and, in contrast to the situation observed in adults, a synthesis rate of 5‐HT very near its maximal value.

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