Tumor renal

Synaptophysin —/+, Actin —/+, Desmin —/+, Myoglobin —, CD34 —, SlOO — 

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Glucocorticoids have inhibitory (apoptotic) effects on lymphocyte proliferation and are used to treat leukemias and lymphomas. Estrogens (fosfestrol) are used to block the effect of androgens in prostate cancer. Progestogens (megestrol, medroxyprogesteroneacetate) have been useful for treating endometrial carcinoma, renal tumors, and breast cancer. 

An increased incidence of renal tumors (7 out of 25 combined adenomas and carcinomas) was observed in male Swiss mice fed 0.1% basic lead acetate in the diet for 2 years (Van Esch and Kroes 1969). No renal tumors were found in the control animals. One female in the 1.0% treatment group had a renal tumor. The authors attributed the low tumor incidence in the 1.0% group to early mortality. The cancer effects levels described above are recorded in Table 2-4 and plotted in Figure 2-2. 

Van Esch EJ, Kroes R. 1969. The induction of renal tumors by feeding basic lead acetate to mice and hamsters. BrJ Cancer 23 765-771. 

Glomerulonephritis, pyelonephritis, renal infarction, papillary necrosis, renal tumors, kidney stones Pyelonephritis, interstitial nephritis... 

The carcinogenic potential of hexachloroethane has not been evaluated following chronic inhalation or dermal exposure. Hexachloroethane increased the incidence of renal tumors in male rats (NTP 1989) following chronic oral exposure. However, these tumors were associated with renal hyaline droplets and, thus, are unique to male rats. Although kidney damage was present in female rats after lifetime exposures to 80 and 160 ppm hexachloroethane, there was no increase in renal tumors. Liver lesions and liver tumors were found in mice following long-term oral exposure (NTP 1977). 

Cancer. No studies have been conducted in human populations to determine whether mirex or chlordecone causes cancer. However, studies in mice and rats have demonstrated the ability of mirex to cause liver tumors (Innes et al. 1969 NTP 1990 Ulland et al. 1977a), pheochromocytomas (NTP 1990), and rare renal tumors (NTP 1990). A study in mice and rats also showed the ability of chlordecone to increase liver tumors (NC11976). As indicated above, available data on the genotoxicity of mirex and chlordecone indicate that these chemicals do not cause cancer by a mutagenic mechanism but rather by tumor promotion. Both mirex and chlordecone are considered by the DHHS to be substances that may reasonably be anticipated to be carcinogens and by IARC to be possible human carcinogens. EPA has not classified mirex or chlordecone as to their carcinogenicity. 

Zhou Ml, Foy RL, Chitalia VC, Zhao J, Panchenko MV, Wang H, Cohen HT (2005) Jade-1, a candidate renal tumor suppressor that promotes apoptosis. Proc Natl Acad Sci USA 102 11035-11040... 

Hiasa Y, Ito N. 1987. Experimental induction of renal tumors. CRC Crit Rev Toxicol 17 279-343. 

There have been no studies of health effects in children exposed to 3,3 -dichlorobenzidine. We have no information on whether 3,3 -dichlorobenzidine causes birth defects in children. It is unknown whether birth defects would occur in the offspring of pregnant animals that breathed or eaten 3,3 -dichlorobenzidine, or had it on their skin. In studies in which pregnant mice were injected with high amounts of 3,3 -dichlorobenzidine under the skin, the kidneys of their babies did not develop properly and some babies developed renal tumors. However, it is highly unlikely that humans will encounter such exposure conditions. 

High mortality was reported in male rats that received 1,4-dichlorobenzene 5 days a week by gavage in com oil in a 2-year study (NTP 1987). At 300 mg/kg/day, 26 of 50 males (52%) died however, survival of female rats at 600 mg/kg/day was comparable to controls. There was no excess mortality in mice of either sex that received 1,4-dichlorobenzene 5 days a week by gavage in com oil for 2 years at levels up to 600 mg/kg/day (NTP 1987). The high rate of mortality in male rats was probably related, in part, to the severe nephrotoxic effects and renal tumors that were reported in these animals and are described in more detail in Sections 2.22.2 and 2.2.2.8. 

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 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. 

Further analysis of the results of the NTP (1987) bioassay has raised certain questions as to the relevance of the observed renal tumors in male rats and hepatic tumors in mice to the potential carcinogenicity of 1,4-dichlorobenzene in humans. The observation that kidney tumors are induced in male but not female rats in response to exposure to chemicals in addition to 1,4-dichlorobenzene has been the focus of recent... 

In a study conducted on rats, no renal tumors were observed during life-time observation following a 90-day continuous exposure to 750 mg/m JP-5 vapor or to 300 mg/m marine diesel fuel vapor (Bruner 1984). Since this study was not designed to test carcinogenicity, these data have limited usefulness. 

Of 25 workers involved in benzidine manufacture, 13 developed urinary bladder tumors and 4 renal tumors also occurred. The average duration of exposure was 13.6 years, and the average induction time from first exposure to detection of the first tumor was 16.6 years. Initial tumors made their appearance as late as 9 years after cessation of exposure. Airborne benzidine concentrations were estimated to have ranged from 0.005 to 17.6mg/m It is not known whether the cancers were influenced by concurrent exposure to other chemicals in the occupational environment. ... 

Mendel rats supports chronic renal tubule injury as the mode of action underlying the renal tumor response. Toxicol Set 53(2) 237-44, 2000... 

Gavage administration of 590 and 1179mg/kg/day to mice for 78 weeks caused a significant increase in the incidence of hepatocellular carcinomas, whereas no increase in these tumors was observed in rats given 212 or 423 mg/kg/day. A nonsignificant increase in renal tumors was seen in rats, and tubular nephropathy occurred in both species. In 2-... 

There are several reports that certain lead compounds, including lead acetate and lead phosphate, administered to animals in high doses are carcinogenic, primarily producing renal tumors.(Note Those salts demonstrating carcinogenicity in animals are soluble, whereas human beings are primarily exposed to insoluble metallic lead and lead oxide.)... 

Boyland E, Dukes CE, Grover PL, Mitchley BCV The induction of renal tumors by feeding lead acetate to rats. Br J Cancer 16 283-288, 1962... 

Chronic animal studies have also yielded varying results. Intratracheal implantation of lead chromates in rats failed to significantly increase the carcinogenic response after 2 years. Intrapleural administration caused a 9% incidence of lung tumors in rats within 19-21 months. Intramuscular injection resulted in lymphomas, renal tumors, fibrosarcomas, and rhabdomyosarcomas at the site of injection in rats. ... 

DMN is clearly carcinogenic, producing tumors in a number of animal species at relatively low doses. Swiss mice fed a diet containing 0.005% DMN for 1 week developed tumors of the kidney and lung. Hamsters fed a diet containing 0.0025% for 11 weeks developed liver tumors. A consistent observation after oral administration of DMN in rats has been that long-term treatment with doses compatible with a favorable survival rate leads to liver tumors, whereas short-term treatment with high doses produces renal tumors. ... 

Progestins, steroid compounds similar to progesterone, such as hydroxyprogesterone caproate (28.3.6), medroxyprogesterone acetate (28.3.7), and megestrol acetate (28.3.7), are used for palliative treatment of breast carcinomas and renal tumors. Progestins can have a direct local effect on cells, and can simultaneously lower the quantity of leutenizing hormone. 

Carcinogenesis In rats, acarbose treatment resulted in a significant increase in the incidence of renal tumors (adenomas and adenocarcinomas) and benign Leydig cell tumors. Further studies showed that the increased incidence of renal tumors found in the original studies did not occur. 

No epidemiological studies of hexachlorobutadiene are available. The occurrence of renal tumors after chronic oral exposure in rats suggests carcinogenicity may be an area of concern following occupational exposure to hexachlorobutadiene and long-term exposures from waste sites. 

N. Lawrentschuk, A.M. Poon, S.S. Foo, L.G. Putra, C. Murone, I.D. Davis, D. M. Bolton, A.M. Scott, Assessing regional hypoxia in human renal tumors using F-fluoromisonidazole positron emission tomography, BJU Int. 96(4) (2005) 540-546. 

Short BG, Swenberg JA. 1988. Pathologic investigations of the mechanism of unleaded gasoline-induced renal tumors in rats. CUT Activities 8(7) 1-6. 

Hard, G.C., Whysner, J., English, J.C., Zang, E. Williams, GM. (1997) Relationship of hydro-quinone-associated rat renal tumors with spontaneous chronic progressive nephropathy. Toxicol. Pathol., 25, 132-143... 

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