Kidney adenocarcinoma

In a carcinogenicity study, Swiss mice were exposed to 10 or 2 5 ppm 4 hours/day, 5 days/ week for 52 weeks. After 98 weeks, 2 5 ppm had caused kidney adenocarcinomas in 24 of 150 males and 1 of 150 females whereas none were seen in the control group. Rats exposed to 75 ppm 6 hours/day, 5/days week for 18 months and then held until 24 months showed a reversible hepatocellular fatty change but no increase in tumor incidence that could be attributed to VDC exposure. Several other studies in other strains of mice, rats, and hamsters did not produce carcinogenic effects. ... 

Vinylidene chloride was tested for carcinogenicity in mice and rats by oral administration and by inhalation, in mice by subcutaneous administration and by topical application, and in hamsters by inhalation. Studies in mice and rats by oral administration gave negative results. In inhalation studies, no treatment-related neoplasm was observed in rats or hamsters. In mice, a treatment-related increase in the incidence of kidney adenocarcinomas was observed in male mice, as were increases in the incidence of mammary carcinomas in females and of pulmonary adenomas in male and female mice. In skinpainting studies in female mice, vinylidene chloride showed activity as an initiator, but, in a study of repeated skin application, no skin tumom occurred. No tumour at the injection site was seen in mice given repeated subcutaneous administrations (lARC, 1986). 

Dichloroethylene has been shown to cause mammary tumors in both rats and mice and kidney adenocarcinomas in mice (3). This compound was found only once during the survey, but it was found at 20 /zg/L in treated water, a level significantly higher than the WHO action limit. Further investigation is necessary to determine the significance of this observation. 

Kidney adenocarcinoma was found in three male public utility workers (aged 34—56) exposed to unspecified PCBs while servicing and repairing transformers for 5-14 years (Shalat et al. 1989). The workers were employed by the same company during the same period, but the total exposed population was not reported. Although kidney cancer is relatively rare in young men (range,... 

Renal epithehal neoplasias, histologically similar to human kidney adenocarcinoma, were found in over one-half of rats ingesting 1.0 ppm aflatoxin Bi and about one-quarter of rats given 0.5 or 0.25 ppm for 147 days (Epstein et al. 1969). 

The lead-induced nephropathy observed in humans and rodents shows a comparable early pathology (Goyer 1993). However, in rodents, proximal tubular cell injury induced by lead can progress to adenocarcinomas of the kidney (see Section 2.2.3.8). The observation of lead-induced kidney tumors in rats may not be relevant to humans. Conclusive evidence for lead-induced renal cancers (or any other type of cancer) in humans is lacking, even in populations in which chronic lead nephropathy is evident. 

Polarising Caco-2 LLC-PK1 MDCK Human colon adenocarcinoma, epithelial, enterocyte-like Porcine kidney, epithelial, proximal tubule cell-like Canine kidney, epithelial, distal tubule cell-like... 

Other cell lines used in permeability studies include the T84 human colonic adenocarcinoma colonic crypt cell model. This line has a reduced carrier expression, secrets mucus, and has very high resistance [31, 32], The IEC cell line is a rat fetal intestinal epithelium cell with higher permeabilities than Caco-2 cells [33], LLC PKi is a pig kidney epithelial cell line with low expression of efflux systems, but expression systems for transport proteins [32], 2/4/A1 cells are a conditionally immortalized rat fetal intestinal epithelium line with crypt cell-like morphology and temperature-sensitive differentiation [34], They form differentiated monolayers with tight junctions, increased brush border enzymes when grown on extracellular matrices with laminin. Transport of drugs with LP in 2/4/A1 monolayers was comparable to that in the human jejunum and up to 300 times faster than that in Caco-2 monolayers. In contrast, the permeability of HP drugs was comparable in both cell lines [34],... 

There was a statistically significant compound-related increase in incidence of several other tumors in female mice hemangiosarcoma of the abdominal retropehtoneum, particularly involving the area of the ovaries, uterus, kidneys, and adrenal subcutaneous fibrosarcomas and mammary adenocarcinoma (NTP 1982). A limitation of the study was poor survival in male mice from ascending suppurative urinary tract infections. 

In studies conducted using animals, evidence of carcinogenicity from 1,4-dichlorobenzene exposure is based on 2-year oral studies in mice and rats. 1,4-Dichlorobenzene was administered by gavage to male rats at doses of 150 mg/kg/day and 300 mg/kg/day, and to female rats and mice of both sexes at doses of 300 mg/kg/day and 600 mg/kg/day. There was a dose-related increase in the incidence of tubular cell adenocarcinomas of the kidneys of male rats. There were no tubular cell tumors in dosed or vehicle-control female rats. There was a marginal increase in the incidence of mononuclear cell leukemia in dosed male rats compared with either vehicle controls or historical controls (NTP 1987). Based on the finding of renal tumors in this study, 1,4-dichlorobenzene was found to be carcinogenic in male rats. 

In chronic studies, DMMP was administered by gavage in corn oil for up to 2 years at doses of 500 or 1000 mg/kg/day to rats and at doses of 1000 or 2000mg/kg/day to mice. " Survival in dosed male rats was reduced, due in part to renal toxicity. Lesions of the kidney included increased severity of spontaneous age-related nephropathy including calcification, hyperplasia of the tubular and transitional epithelium, tubular cell adenocarcinomas, and transitional cell papillomas and carcinomas. Similar lesions were not seen in female rats or in mice of either sex, although reduced survival in male mice prevented adequate analysis. The... 

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... 

Chronic study (mouse) Mammary gland adenocarcinoma, liver necrosis, urinary bladder hyperplasia (640 mg kg-1 per day) Kidney lesions (62.5 mg kg-1 per day)... 

Kidney tumors caused by several different compounds, including 1,4-dichlorobenzene, isophorone, and unleaded petrol, have been found to be both sex dependent and species dependent. Thus, only male rats suffer from oc2-p-globulin nephropathy and renal tubular adenocarcinoma as a result of the accumulation of a compound-protein complex in the epithelial cells of renal proximal tubules (see chap. 6). The synthesis of the protein involved, a2-[i-globulin, is under androgenic control in the male rat. 

Ear canal Kidney Small Colon Total Adenocarcinoma Adenoma... 

Dichloroacetylene was tested for carcinogenicity in mice and rats by inhalation. A treabnent-related increase was observed in the incidence of adenocarcinomas of the kidney in male mice. In rats, the occurrence of benign tumours of the liver and kidney and an increased incidence of lymphomas were reported (lARC, 1986). 

Bioenergetic dysfunction of mitochondria has been reported as a hallmark of many types of cancers (i.e., downregulation of ATP synthase /3-subunit expression in liver, kidney, colon, squamous esophageal, and lung carcinomas, as well as in breast and gastric adenocarcinomas). ATP synthase d-subunit was found to be associated with chemoresistance to 5-fluorouracil (5-FU) in CRC using 2D-PAGE. In a functional assay, suppressed ATP synthase d-subunit expression by siRNA transfection increased cell viability in the presence of 5-FU [115]. 

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