Liver cell neoplasms

A recent study confirmed that ethylene thiourea was carcinogenic in male and female rats as shown by increased incidences of thyroid follicular cell neoplasms after treatment of up to 250 ppm in the diet for 2 years. In mice, concentrations ranging from 100 to 1000 ppm for 2 years caused liver and pituitary tumors in addition to thyroid tumors. Perinatal exposure up to 8 weeks followed by a control diet for 2 years was not carcinogenic in rats or mice. Combined perinatal-adult ETU exposures produced the same carcinogenic effects as adult-only exposures. 

Measurement of serum y-GT activity has clinical significance. The enzyme is present in all tissues, but the highest level is in the kidney however, the serum enzyme originates primarily from the hepatobiliary system. Elevated levels of serum y-GT are found in the following disorders intra- and posthepatic biliary obstruction (elevated serum y-GT indicates cholestasis, as do leucine aminopeptidase, 5 -nucleotidase, and alkaline phosphatase) primary or disseminated neoplasms some pancreatic cancers, especially when associated with hepatobiliary obstruction alcohol-induced liver disease (serum y-GT may be exquisitely sensitive to alcohol-induced liver injury) and some prostatic carcinomas (serum from normal males has 50% higher activity than that of females). Increased activity is also found in patients receiving phenobarbital or phenytoin, possibly due to induction of y-GT in liver cells by these drugs. 

Neoplasms that are essentially negative with most CEA antibodies include adenocarcinomas of prostate, kidney, adrenal gland, and endometrium,220 along with serous ovarian tumors and mesotheliomas. Liver cell-derived tumors are nonreacti ve with the monoclonal CEA antibodies but do react with the polyclonal antibodies... 

Liver and Gallbladder. High dosages of oral estrogens have been reported to increase the risk for jaundice, cholestatic hepatitis, gallstones, and hepatic vein blood clots. Estrogens promote the development of hepatic neoplasms associated with increased hepatic cell regenerative activity (186,187). 

Four of four beagle dogs administered DCB by capsule for 7 years had bladder papillary transitional cell carcinoma and three had liver carcinoma untreated controls had no liver or bladder neoplasms. ... 

In rat liver, 1,2-dimethylhydrazine had no consistent effect on the relative focal volume of y-glutamyltranspeptidase-positive preneoplastic foci (Denda et al., 1988). Locniskar et al. (1985) treated Brown-Norway and Fischer rats with 150 mg/kg bw 1,2-dimethylhydrazine by gavage five times over a three-week period. Five months after the final treatment, isolated splenic, colonic intraperithelial lymphocytes and lamina propria lymphocytes from the Brown-Norway strain exhibited low natural killer cell activity and reduced splenic T-lymphocyte proliferation in response to autologous non-T lymphocytes. Furthermore, colonic lamina propria lymphocyte proliferation was low, and Brown-Norway rats had a low incidence of 1,2-dimethylhydrazine-induced colonic neoplasms (7%) in comparison with Fischer rats, which had more effective splenic and colonic intraperithelial lymphocyte natural killer cell activity, enhanced splenic autologous mixed lymphocyte response, enhanced colonic lamina propria lymphocyte proliferation and a higher incidence of colon tumours (20%). 

The presence of this artifact poses a distinct risk of its being interpreted as positive staining, as the artifact can be intense and may be precisely located in the cells of interest with a clean background. It is known that liver and kidney can retain high amounts of retrievable biotin-avidin activity in neoplasms. The need for adequate controls or biotinblocking procedures is obvious when histochemical or immunohistochemical procedures are used. Negative controls facilitate identification of such nonspecific staining. 

DR has been shown to delay onset of a number of other spontaneous tumors in rodents. This includes hepatoms, breast tumors, pancreatic islet cell tumors, renal tumors, mammary gland cancers, pituitary tumors, and pheochromocytomas. Decrease in spontaneous appearance of preneoplastic foci in the liver was observed in the SPF Wistar rats. Similarly, marked reduction in spontaneous hepatoma was observed in B6C3F1 mice diet restricted for 12 months. In rodents, DR has been shown to decrease colon cancer incidence. Recently it has been shown that DR prevents spontaneous sarcomas and lymphomas in p53 mice, which are genetically susceptible to a number of neoplasms. The decrease in tumor incidence is linked to the increase in life expectancy of DR animals, especially rodents, where the incidence of spontaneous tumors is the leading cause of death in rodents. 

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