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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal carcinoma in male Syrian hamsters, induced by chronic administration of estradiol for 5-7 months, is known to arise in the cortex at the cortico-medullary junction. In this in vivo model for hormonal carcinogenesis, estrogen-induced covalent DNA adducts have previously been observed in whole kidney and have been postulated to be involved in tumor induction. In the present study, the intrarenal distribution of estrogen-induced DNA modification and estrogen metabolizing enzymes were investigated in male Syrian hamsters to ascertain a role of metabolism and adduct formation in estrogen-induced carcinogenesis. The highest estrogen-induced DNA adduct concentrations as measured by 32P-postlabeling analysis were found in the renal cortex of hamsters treated with estradiol for 7 months. Total adduct levels in medullary DNA were approximately one-half of those found in cortex. Cytochrome P-450 enzymes were detected only in microsomes of kidney cortex (approximately 0.8 +/- 0.6 nmol P-450/mg protein) but not medulla of untreated male Syrian hamsters. Prostaglandin endoperoxide synthase activity in kidney cortical microsomes was 1/5 of the activity found in medullary microsomes. Thus, microsomal cytochrome P-450 levels and estrogen-induced DNA adduct formation were highest in hamster kidney cortex, the origin of renal tumorigenesis. It is postulated that estrogen metabolism by cytochrome P-450 enzymes leading to covalent DNA modification plays a role in hormonal carcinogenesis in the hamster kidney.
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PMID:Localization of estrogen-induced DNA adducts and cytochrome P-450 activity at the site of renal carcinogenesis in the hamster kidney. 310 11

In order to develop a high-frequency, single-dose model of renal epithelial tumor induction in the mouse, streptozotocin (250 mg/kg) was administered i.v. to 6-week-old males and females of the CBA/H/T6J strain. In groups of 26 males and 30 females representing the effective number of survivors eligible for tumor estimates, renal cell tumors were found in 73% of males and 97% of females, including incidences of lesions diagnosed as renal carcinoma in 31 and 60%, respectively. The difference in renal tumor frequency between the sexes was not considered a real effect owing to the significantly decreased survival of the males. The neoplastic lesions ranged from small papillary or cystopapillary adenomas with a benign appearance to large, solid carcinomas with a low potential for metastasis. In the females, 22% of the larger tumors metastasized to distant sites, mainly the lungs. Intermediate lesions incorporating both papillary and solid adenomatous profiles suggested a sequential development of carcinomas along this pathway from the smaller papillary foci. The data establish the administration of a single dose of streptozotocin in the female CBA/H/T6J as a suitable high incidence model for the study of renal epithelial carcinogenesis in the mouse.
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PMID:Identification of a high-frequency model for renal carcinoma by the induction of renal tumors in the mouse with a single dose of streptozotocin. 315 46

Estrogens have previously been shown to induce covalent DNA modifications specifically in the hamster kidney, the target organ of estrogen-inducible and -dependent renal carcinoma. The DNA adducts, formed by yet unknown mechanisms, have been postulated to mediate hormonal carcinogenesis in this animal model. In an attempt to study a possible involvement of estrogen receptor mechanisms in the formation of DNA adducts, 17 beta-estradiol and the antihormone tamoxifen were concomitantly administered as s.c. implants to male Syrian hamsters. 17 beta-Estradiol-treated and tamoxifen-treated animals served as positive and negative controls, respectively. The tumor incidence decreased from 100% in 17 beta-estradiol-treated controls to 25% in the group receiving tamoxifen in addition to hormone. Tamoxifen-treated animals did not develop kidney tumors and did not show any detectable DNA damage. DNA adduct levels were comparable in hamsters treated with 17 beta-estradiol and 17 beta-estradiol plus tamoxifen for 5 or 7 months. In hamsters inoculated with H-301 cells, which are derived from the estrogen-induced hamster renal carcinoma and are estrogen dependent for growth, tamoxifen decreased estrogen-dependent H-301 tumor growth. However, in cell culture, neither 17 beta-estradiol nor tamoxifen influenced H-301 cell division. It was concluded that tamoxifen inhibited the growth of estrogen-induced renal carcinoma but did not interfere with tumor initiation since it did not inhibit the formation of DNA adducts. Moreover, receptor mechanisms were most probably not involved in the induction of DNA modifications by estrogens.
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PMID:Inhibition of estrogen-induced renal carcinogenesis in male Syrian hamsters by tamoxifen without decrease in DNA adduct levels. 333 75

The development and maintenance of DNA hypomethylation were investigated in male Syrian hamsters during the course of induction of renal carcinoma by estrogens and in an estrogen-dependent tumor derived from H-301 cells. The H-301 cell line was obtained from a primary renal carcinoma induced by E-diethylstilbestrol treatment. Covalent DNA modifications in estrogen-exposed kidney and tumor tissues were also examined. The five tumors investigated were induced by s.c. estrogen treatment of animals for 7-9 months. Covalent DNA adducts were detected in kidneys after 5-7 months of exposure to various estrogens, but not in primary tumors induced by estrogen treatment for 7-9 months. Estrogen-induced covalent DNA modifications likewise were not detectable in tumors grown in estrogenized hamsters inoculated with H-301 cells. In contrast, DNA was hypomethylated in primary tumors induced by E-diethylstilbestrol, estradiol or 11 beta-ethyl-17 alpha-ethinyl estradiol, but not in untreated and estrogen-exposed kidney. Compared with kidney tissue, there was an 11-24% decrease in total genomic DNA methylation in the estrogen-induced and -dependent tumors. DNA hypomethylation was maintained in tumors derived from H-301 cells. Discontinuation of estrogen treatment rapidly decreased the size of estrogen-dependent H-301 tumors, but did not affect the degree of DNA hypomethylation. Thus, DNA hypomethylation occurred in hormone-dependent primary neoplasms and was maintained after serial transplantations independent of the growth status.
Carcinogenesis 1988 Jun
PMID:Hypomethylation of DNA in estrogen-induced and -dependent hamster kidney tumors. 337 Jul 56

In animals and humans, estrogens are able to induce cancer in susceptible target organs, but the mechanism(s) of estrogen-induced carcinogenesis has not been elucidated. A well-known animal model is the development of renal carcinoma in estrogen-treated Syrian hamsters. Previous work demonstrated the presence of covalent DNA addition products (adducts) in premalignant kidneys of hamsters exposed to the synthetic estrogen, diethylstilbestrol, a known human carcinogen. In the present study, the natural hormone, 17 beta-estradiol, and several synthetic steroid and stilbene estrogens were examined by a 32P-postlabeling assay for their capacity to cause covalent DNA alterations in hamster kidney. Chronic exposure to each of the estrogens tested led to the gradual formation of five chromatographically distinct unusual nucleotides specifically in kidney DNA. Irrespective of the estrogen used, chromatograms exhibited identical mobilities of each of these adducts in seven different systems on PEI-cellulose anion-exchange TLC, in three different conditions on reversed-phase TLC, and in one system on silica gel partition TLC. Therefore, the DNA adducts observed did not contain moieties derived from the structurally diverse estrogens. It is concluded that each of the estrogens induced the binding of the same unknown endogenous compound (or compounds) to target tissue DNA. This novel property of estrogens is postulated to play a key role in hormone-induced malignancy.
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PMID:Estrogen-induced endogenous DNA adduction: possible mechanism of hormonal cancer. 346 92

To elucidate the localization of enolase isozymes in renal tubules and renal cell carcinoma, an immunohistochemical study and quantitative analysis by employing the enzyme immunoassay were performed. The alpha-enolase was localized in almost all epithelial cells of renal tubules except for loops of Henle. The gamma-enolase was localized in macula densa cells and epithelial cells of loops of Henle and collecting ducts of the medulla, but not in those of proximal tubules. In renal cell carcinoma, most tumor cells possessed two enolase isozymes. From these immunohistochemical findings, it is suggested that enolases are present mainly in the alpha alpha form in epithelial cells of proximal tubules, in the gamma gamma form in those of loops of Henle, and in the two forms and/or the alpha gamma form in tumor cells of renal cell carcinoma. The levels of gamma-enolase in the normal cortex were 16.8 +/- 3.7 ng/mg protein (n = 7), whereas those in renal cell carcinoma were 928 +/- 554 ng/mg protein (n = 7), about 55-fold higher than those in the normal cortex. The serum gamma-enolase levels were also enhanced in 20 (49%) of 41 patients with renal cell carcinoma. Because it is generally accepted that renal cell carcinoma is derived from epithelium of proximal tubules, the expression of gamma-enolase has occurred during carcinogenesis.
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PMID:Enolase isozymes in renal tubules and renal cell carcinoma. 376 7

Estrogens are known to induce tumors in several animal species. To understand the mechanism of hormonal carcinogenesis, estrogen-induced renal carcinoma in male Syrian hamsters was investigated using estradiol and 2-fluoroestradiol. The biological activities of the latter steroid were compared with those of the natural hormone, because of the reduced metabolic conversion of 2-fluoroestradiol to catechol estrogen metabolites. 2-Fluoroestradiol was administered to male Syrian hamsters at three times the dose (60 mg) of estradiol (20 mg, positive control) by s.c. implantation. After 7 months, 75% of the estradiol-treated hamsters had kidney tumors, while in animals exposed to 2-fluoroestradiol renal carcinoma could not be detected. The reduced tumor incidence by the fluorinated steroid is not due to a lack of estrogenic potency. In the test animals, pituitary LH concentrations matched those measured in estradiol-treated hamsters and the reduction in testes weights was comparable. Furthermore, in immature female rats, uterine wet weight increases illustrate that 2-fluoroestradiol is a potent estrogen. The observed increases in uterine weight were shown to be accompanied by increases in protein and DNA synthesis comparable to those observed in estradiol-treated animals. 2-Fluoroestradiol stimulated growth of H-301 cells in vivo. These cells are estrogen-dependent for growth and are derived from the primary hamster kidney tumor. The results indicate that hormonal activity and carcinogenicity of estrogens are separable properties.
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PMID:Hormonal carcinogenesis: separation of estrogenicity from carcinogenicity. 376 51

Acquired multicystic renal transformation of diseased kidneys is a problem known since the early 19th century which has recently regained interest. Such cysts were known before dialysis was established, are seen prior to hemodialysis and in patients on peritoneal dialysis, and can therefore not be a consequence of hemodialysis. It is concluded that an increased incidence of renal cell carcinoma in such kidneys is not established, although, theoretically, several mechanisms might promote carcinogenesis in end-stage kidneys.
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PMID:Acquired multicystic transformation of kidneys. 391 9

The synthetic estrogen diethylstilbestrol (DES), a known human carcinogen, induces renal carcinoma in male Syrian hamsters within 6 months after s.c. implantation. Tumor formation could be evoked by its hormonal properties or by a reactive genotoxic metabolite binding to DNA, but previous attempts to detect adducts have failed. In the present study, kidney DNA of male Syrian hamsters, treated with s.c. DES implants to induce renal carcinoma, was analyzed for the presence of DES-induced adducts using 32P-postlabeling assay. Covalently-modified DNA nucleotides were detected in the kidneys after chronic DES treatment, but not in kidneys of untreated hamsters, or in liver or tumor tissue of DES-treated animals. This report demonstrates for the first time the ability of an estrogen to give rise to covalent DNA modification in vivo specifically in the target organ of carcinogenesis. DES-induced covalent DNA adducts are taken as evidence for tumor initiation by DES via damage to cellular macromolecules, in addition to tumor-promotional effects described previously.
Carcinogenesis 1985 Jul
PMID:Target organ-specific covalent DNA damage preceding diethylstilbestrol-induced carcinogenesis. 401 74

Homogenates of human renal cell carcinomas were tested for glutathione-S-transferase, an enzyme of normal proximal tubule cells. All tumors were positive; mean tumor fraction enzyme activity was 0.040 +/- 0.02 mumol/min/microgram protein. Glutathione-S-transferase activity in homogenates from normal kidney was 0.022 and 0.054 mumol/min/microgram protein. Finding similar levels of a major cytosolic enzyme in tumor and renal cortex confirms the origin of renal cell carcinoma in the proximal nephron. Glutathione-S-transferase, which binds carcinogens and steroids, may play a role in carcinogenesis and serve as a marker for this tumor.
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PMID:Glutathione-S-transferase in human renal cell carcinoma. 405 74


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