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The processing pathway of G-proteins and Ras family proteins includes the isoprenylation of the cysteine residue, followed by proteolysis of three terminal residues and alpha-carboxyl methyl esterification of the cysteine residue. Farnesylcysteine methyltransferase (FCMT) activity is responsible for the methylation reaction which play a role in the membrane attachment of a variety of cellular proteins. Four kinds of Ras protein (c-Ha-ras, c-N-Ras, c-Ki-Ras, pan-Ras) expression were detected in adenocarcinoma of human tissue by immunohistochemical method, and hematoxylin and eosin staining. The level of Ras protein in human stomach tumor tissues was much higher than in normal and peritumoral regions of the same biopsy samples. The FCMT activities of each cellular fractions were high in mitochondrial fraction followed by microsomal fraction, whole homogenate and cytosolic fraction. The inhibitory effect on FCMT activity on stomach tumor tissue was determined after treatment with 0.25 microM of S-adenosyl-L-homocysteine. S-adenosyl-L-homocysteine inhibited FCMT activity from 11.2% to 30.5%. These results suggested that FCMT might be involved in Ras proteins activity.

In the self-fertilizing hermaphroditic fish, Rivulus marmoratus, the susceptibility to tumor induction by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was evaluated. Seven-day-old fish larvae were exposed for 2 h to MNNG at concentrations ranging from 5 to 25 ppm in a static water bath. The exposed fish were observed at 2 and 4 months after carcinogen treatment to assess tumor development. Within 4 months after 25 ppm MNNG exposure, nearly all fish developed thyroid tumors. The tumor incidences were dose- and time-dependent, and the latent period of tumor induction was less than 2 months. Most induced neoplasms were papillary carcinomas similar histologically to those of rodents and humans, and the tumors were serially transplantable to other fish of the same species. These results demonstrate that rivulus could be useful as a model of thyroid carcinogenesis.