Adenoma tubular

In an earlier study, there were renal tubular cell adenomas in 5/50 Osbome-Mendel rats receiving doses of 212 mg/kg/day but no tumors in 49 animals receiving 423 mg/kg/day or in 20 vehicle control rats (Weisburger 1977). Despite the lack of tumors, there was a high incidence of nephropathy (18-66%) in exposed male and female rats. 

M (CEL tubular cell adenoma NC11976 and carcinoma tubular cell Dunnick and neoplasms in 4/50)... 

As shown in Table 2-2, 300 mg/kg/day is the cancer effect level (CEL) for renal tubular cell adenomas in male rats and 600 mg/kg/day is the CEL for hepatocellular carcinomas and hepatoblastomas in mice (NTP 1987). A qj (the upper-bound estimate of the low-dose slope of the dose-response curve as determined by the multistage procedure) of 6x10 per mg/kg/day has been calculated from the data on renal tumors in rats (Battelle and Crump 1986). The qi for the mouse liver tumor data is 2.4x10 per mg/kg/day (HEAST 1992). These values are currently under review by the EPA (HEAST 1990) and have not been included in the IRIS (1998) database. 

In 2-year studies rats were given 0, 25, or 50mg/kg hydroquinone by gavage 5 days/ week whereas doses for mice were 0, 50, or lOOmg/kg on the same schedule. There was evidence of carcinogenicity in male rats as indicated by increased incidences of tubular cell adenomas of the kidney, in female rats as shown by increases in mononuclear cell leukemia, and in female mice based on increases in hepatocellular neoplasms, mainly adenomas. There was no evidence of carcinogenicity in male mice. 

A 2-year gavage study at 250 and 500 mg/ kg demonstrated a dose-related statistically significant excess of tubular cell adenomas and adenocarcinomas of the kidney in male rats, a number of preputial gland tumors in dosed male rats, and a probable increased incidence of hepatocellular neoplasms in high-dose male... 

Two-year studies were conducted by administering VCD in acetone by dermal application 5 days per week for over 100 weeks to groups of rats of each sex at 0, 15, or 30mg/animal and to groups of mice at 0, 2.5, 5, or lOmg/animal. Acanthosis and sebaceous gland hypertrophy of skin from the scapula were observed at increased incidences in both species. Squamous cell papillomas in male rats and squamous cell carcinomas in males and females were observed in exposed rats at an increased incidence. The combined incidence of basal cell adenomas or carcinomas was also increased in both sexes. Squamous cell carcinomas were found in the exposed mice. Follicular atrophy and tubular hyperplasia of the... 

Carcinogenesis An increased incidence of renal tubular adenomas and carcinomas was found in male rats treated with the highest dose of entacapone. 

Studies in rats reported renal tubular adenomas and adenocarcinomas in male and female animals at doses of 20 mg/kg/day (Kociba et al. 1977a). Metastasis to the lungs was observed. Combined incidences of renal tubular neoplasms in males (9/39, 23%) and in females (6/40, 15%) increased (p <0.05) over controls (males-1/90, females-0/90, 0%). The tumor incidence was not increased in the 0.2 and 2 mg/kg/day dose groups but there were some indications of hyperplasia in animals exposed to 2 m /kg/day. The EPA (1990f) evaluated these data and calculated a human potency factor of 7.8x10 (mg/kg/day) (qi ), representing 95% upper confidence limit of extra lifetime human risk. Based on this value, cancer risk levels of 10, 10, and 10 correspond to exposures of 0.001, 0.0001, 0.00001 mg/kg/day. 

Cancer. Increased incidences of relatively rare renal tubular cell adenomas and carcinomas were observed in male rats, but the increases were not statistically significant by the Fisher Exact test or the Cochran-Armitage test (NTP 1986). When adjusted for mortality, however, the increased incidences were significantly different from control in the high-dose males when analyzed by the Lifetable test and significant for dose-related trend by the Lifetable and the Incidental Tumor tests. 

Features include muscle weakness and cramps, paraesthesia, nausea, vomiting, constipation, abdominal pain, polyuria, polydipsia, depression, confusion and psychosis. Hypokalaemia may cause brady/tachyarrhythmias, hypotension, respiratory failure, ileus and altered mental state. It also increases the toxicity of cardiac glycosides. There are several associated disease states (e.g. diarrhoea, vomiting, renal tubular acidosis types I and II, hypomagnesaemia, Conn s syndrome, Cushing s disease, Gitelman s syndrome, villous adenoma, pyloric stenosis, intestinal fistulae). 

In 2 year gavage studies, there was clear evidence of carcinogenic activity of D-limonene for male rats, as shown by increased incidences of tubular cell hyperplasia, adenomas, and adenocarcinomas of the kidney. There was no evidence of carcinogenic activity of D-limonene for female rats. There was no evidence of carcinogenic activity of D-limonene for male or female mice. The nephrotoxicity of D-limonene was studied in rats and mice. Kidney sections taken from male rats that had been part of a 91 day oral dosing study of limonene in rats and mice were examined by light microscopy. The study showed that renal alterations were induced only in male rats. As discussed above, the mechanism by which D-limonene caused the tumors in male rats is irrelevant to humans. 

Female rats are also more susceptible than males to such organophosphorus insecticides as azinphosme-thyl and parathion. Castration or estrogen treatment of the male reverses this difference. The male rat is far more susceptible to carcinoma than the female as shown in the following examples Males are more susceptible to the induction of pancreatic tumors by azaserine, colonic carcinoma by dime-thylhydrazine, intestinal tumors by dimethylnitrosa-mine, renal tumors by decalin, and liver cirrhosis by AAF. In the case of hydroquinone, which is present in photographic material, acute exposure produced renal toxicity in the female but in a chronic 2 year study, the male and not the female was found to have tubular degeneration and adenoma. 

Acute exposure to unleaded gasoline and a variety of light hydrocarbons present in gasoline produces a nephropathy in male rats characterized by (1) an excessive accumulation of protein (hyaline droplets) in epithelial cells of proximal tubule, (2) accumulation of casts at the corticomedullary junction, and (3) evidence of mild tubular regeneration. This nephropathy only occurs in male rats female rats and mice do not show any renal pathology. A number of chemicals present in unleaded petrol when tested alone have been shown to produce nephropathy and, in particular 2,2,4-trimethylpentane and decalin have been used as model compounds. Certain other industrial chemicals (1,4-dichlorobenzene and isophorone), natural products (o-limonene), and pharmaceuticals (levamisole) also produce this male-rat-specific nephropathy. Chronic exposure of male rats to unleaded petrol, 1,4-dichlorobenzene, isophorone, or o-limonene ultimately leads to the induction of a low incidence of renal adenomas and carcinomas. 

Chronic 8-MOP administration of up to 75 mg kg for 2 years increases the incidence of renal tubular cell hyperplasia, adenomas, and adenocarcinomas of the kidney and carcinomas of the zymbal gland in male rats. 8-MOP with the addition of UVA induces the development of squamous cell hyperplasia, squamous cell papilloma, squamous cell carcinoma, cutaneous melanoma, and cataracts in rats. 

As a result of National Toxicology Program (NTP) bioassays, PERC has been reported to produce hepatocellular carcinomas in B6C3F1 mice of both sexes when administered by gavage. An NTP inhalation study also showed hepatocellular carcinomas in B6C3F1 mice and renal cell adenomas and adenocarcinomas and mononuclear cell leukemias and renal tubular cell neoplasms in Fisher 344 rats. 

The level of ras oncogene protein product p21 (L6) was evaluated in specimens of normal human colonic mucosa, hyperplastic polyps, tubular adenomas, villous adenomas, and the epithelium from a case of ulcerative colitis. Differences in p21 values among all classes of polyps were significant (hyperplastic polyps had values less than tubular adenoma values, which were less than villous adenoma... 

Most adenomas of the extrahepatic biliary tract (EHBT) occur in the gallbladder and are usually detected incidentally." In contrast, those in the extrahepatic bile ducts (EHBDs) present with signs and symptoms of obstruction. They can be multifocal, especially those with a papillary architecture. On the basis of the growth pattern, they have been classihed traditionally as tubular, papillary, or tubulopapillary, although the relevance of this classihcation independent of the degree of dysplasia is debatable. ... 

Albores-Saavedra J, Sheahan K, O Riain C, ShuklaD. Intraductal tubular adenoma, pyloric type, of the pancreas additional observations on a new type of pancreatic neoplasm. Am J Surg Pathol. 2004 28 233-238. 

Kato N, Akiyama S, Motoyama T. Pyloric gland-type tubular adenoma superimposed on intraductal papillary mucinous m-mor of the pancreas. Pyloric gland adenoma of the pancreas. Virchows Arch. 2002 440 205-208. 

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