INEFFECTIVENESS OF THE PRESENCE OF H-RAS P53 COMBINATION OF MUTATIONSIN SQUAMOUS-CELL CARCINOMA-CELLS TO INDUCE A CONVERSION OF A NONTUMORIGENIC TO A TUMORIGENIC PHENOTYPE/

Human tumor cells have properties in vitro or in surrogate hosts that are distinct from those of normal cells, such as immortality, anchorag e independence, and tumor formation in nude mice. However, different c ells from individual tumors may exhibit some, but not all of these fea tures. In previous years, human tumor cell lines derived from differen t tumor and tissue types have been studied to determine those molecula r changes that are associated with the in vitro properties listed abov e and with tumorigenicity in nude mice. In the present study, seven ce ll lines derived from human tumors were characterized for p53 and ras mutations that may occur in SCC tumor phenotypes and for tumor formati on in nude mice. This investigation was designed to examine whether co -occurrence of mutated ras and p53 lead to a malignant stage in the pr ogression process. None of the seven cell lines contained mutations in the recognized ''hot spots'' of the p53 tumor suppressor gene, but fo ur had a nonsense/splice mutation in codon 126 and a mutation in codon 12 of the H-ras gene. The remaining three cell lines had p53 mutation s in intron 5, in codon 193, and a missense mutation in codon 126, res pectively. Four of seven cell lines were nontumorigenic; two of these cell lines contained a nonsense p53-126 mutation and mutated ras; one had a missense mutation at codon 126 but no mutated ras; the the fourt h had only a p53 mutation at codon 193. Two of the nontumorigenic cell lines were converted to tumorigenicity after treatment with methyl me thanesulfonate or N-methyl-N'-nitro-N-nitrosoguanidine with no apparen t additional mutations in either gene. Our analysis revealed that ther e was a high frequency of genetic diversity and mutations in both p53 and H-ras. There was also a lack of a causal relationship in the prese nce of mutations in p53 and the cells' ability to exhibit a malignant potential in nude mice.