methylnitronitrosoguanidine and Chemical-and-Drug-Induced-Liver-Injury

Histochemical markers are important for the early detection of chemically initiated neoplasia in experimental animal studies. The marker, iron resistance, was evaluated in the Shasta strain of rainbow trout (Salmo gairdneri). Twenty-one-day-old trout embryos were exposed to 100 ppm aqueous N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for 30 min in a static water bath. Fish were fed a semipurified diet, and sampled monthly from the 4th to the 9th month. Two days before sampling, fish were iron-loaded with a single ip dose of 0.30 mg iron dextran/100 g body weight. Livers and kidneys were conventionally processed to paraffin sections for iron, or hematoxylin and eosin (H&E) staining. Normal hepatocytes accumulated iron in pericanalicular locations, but in hepatocytes from carcinogen-altered foci and tumors, iron staining was clearly reduced or absent. Normal renal tubule cells exhibited slight to moderate iron staining, while those from nephroblastoma were iron resistant. These results establish iron resistance as a property of preneoplastic and neoplastic trout hepatocytes and nephroblastoma cells for the first time. Iron resistance may offer a practical histochemical marker in experimental fish models of hepatocellular carcinoma and nephroblastoma.

Topics: Adenoma; Animals; Biomarkers, Tumor; Chemical and Drug Induced Liver Injury; Histocytochemistry; Iron; Kidney Neoplasms; Liver Neoplasms, Experimental; Methylnitronitrosoguanidine; Salmonidae; Trout; Wilms Tumor

A method to make a diverted segment of the colon keeping direct continuity to the main colonic lumen was introduced to study carcinogenesis in the colon of rats. This method was proved to be useful for analyzing several factors influencing upon cancerization in the colonic mucous membrane. Macroscopical colonic neoplasia were induced in nearly 80% of rats treated with N-methyl-N'-nitro-N-nitrosoguanidine introduced into the colonic lumen through the diverted segment. Neoplastic lesion of the mucous membrane developed mainly in the colonic segments which were in direct contact with intestinal content. The importance of intestinal content and colonic microflora was discussed and reviewed. One epithelial cell line was established from one intraperitoneal metastatic deposit of a huge colonic carcinoma induced by the carcinogen. This cell line has been maintained in tissue culture. The liver was susceptible to the carcinogen, and multiple cystic lesions were observed after intracolonic administration of the chemical.

Topics: Adenoma; Animals; Chemical and Drug Induced Liver Injury; Colon; Colonic Neoplasms; Cysts; Female; Liver; Liver Diseases; Male; Methylnitronitrosoguanidine; Mitosis; Neoplasm Metastasis; Neoplasms, Experimental; Rats