methylnitronitrosoguanidine and Adenoma--Bile-Duct

The modifying effects of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a mutagenic by-product in chlorinated water, on the development of glandular stomach cancers were investigated in Wistar rats. A total of 120 males, 6 weeks of age, were divided into six groups. After initiation with 100 ppm N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) solution and 5% NaCl diet for 8 weeks, 30 rats each in groups 1-3 were given MX in the drinking water at concentrations of 30, 10, or 0 ppm for the following 57 weeks. Ten animals each in groups 4-6 were administered the MX without prior carcinogen exposure. There were no statistical significant differences in final body weights between the groups. The incidences and multiplicities of adenocarcinomas in the glandular stomachs were significantly higher (P < 0.05) in the initiated 30 ppm MX group than those in the MNNG/NaCl group. The incidences of atypical hyperplasias in the glandular stomachs were also significantly increased (P < 0.05 or 0.01) by the MX treatments. With their multiplicity, the effects were clearly dose dependent. Interestingly, the 30 ppm MX alone itself induced atypical hyperplasias in the pylorus, although the incidences and severity were low. Moreover, MX showed a tendency to enhance the development of intrahepatic cholangiocellular tumors and thyroid follicular cell tumors in the MNNG-treated animals. The results of the present study thus indicate that MX exerts promoting effects when given during the postinitiation phase of two-stage glandular stomach carcinogenesis in rats.

Topics: Adenocarcinoma; Adenocarcinoma, Follicular; Adenoma, Bile Duct; Animals; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Body Weight; Carcinogens; Cholangiocarcinoma; Cocarcinogenesis; Fibrosis; Furans; Hyperplasia; Male; Methylnitronitrosoguanidine; Mutagens; Organ Size; Precancerous Conditions; Pylorus; Rats; Rats, Wistar; Stomach; Stomach Diseases; Stomach Neoplasms; Thyroid Neoplasms; Water Pollutants, Chemical

The histology and ultrastructure of more than 100 tumors produced by a chemically transformed rat liver epithelial cell line and its single-cell-derived clonal subpopulations were studied. Wide-ranging morphologic presentations were observed, including carcinomas, sarcomas, "mixed epithelial-mesenchymal" tumors, and undifferentiated tumors. In addition to epidermoid and adenocarcinomas, several tumors were morphologically indistinguishable from hepatocellular carcinomas. The "mixed epithelial-mesenchymal" tumors reproduced most of the various histologic features of human hepatoblastomas. In many instances, the epithelial component occupied focal areas of tumors, and transmission electron microscopic studies of the "sarcomatous" regions revealed either spindle-shaped epithelial tumor cells or, in most cases, scattered epithelial tumor cells surrounded by numerous fibroblasts or myofibroblasts. Similar findings were observed in several "sarcomas" examined ultrastructurally, which suggests that most of the mixed tumors or sarcomas actually were spindle cell carcinomas and/or carcinomas with marked host fibroblastic reaction. However, in a few mixed tumors produced by clonally derived cell strains, unequivocal carcinosarcomas with neoplastic osteoid or chondroid tissue were demonstrated. The findings of this study are discussed in the context of current insights on the cellular composition of the liver and on the histogenesis of human hepatoblastoma.

Topics: Adenoma, Bile Duct; Animals; Cell Line; Cell Transformation, Neoplastic; Liver Neoplasms; Liver Neoplasms, Experimental; Methylnitronitrosoguanidine; Microscopy, Electron; Neoplasm Metastasis; Neoplasm Transplantation; Rats; Sarcoma, Experimental