Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of splenectomy on carcinogenesis by a single 10-mg dose of 7,12-dimethylbenz[alpha]anthracene (DMBA) given in olive oil by gavage was tested on BTOs, C57BL/60s, C3H/HeOs, and BALB/cOs mice. The splenectomy, performed a week before the DMBA was given, did not affect physical status or the incidence of acute toxic death of animals. DMBA-treated animals developed neoplasms at a significantly higher rate than did untreated mice. Splenectomy did not influence the overall incidence of neoplasms. Observed tumors in DMBA-treated groups were those of skin, forestomach, colon, liver, lung, adrenal, ovary, breast, hematopoietic-lymphoreticular system, and vascular system, depending on the strain. Types of DMBA-treated neoplasms were affected by prior splenectomy, depending on the strain: Splenectomy inhibited lung adenomas in BALB/cOs females and hepatomas in C57BL/60s females; splenectomy enhanced skin neoplasms in C57BL/60s and squamous cell carcinoma of the forestomach in BTOs males. The most significant change was in the incidence of the group of lymphomas. Myelogenous leukemia was increased in DMBA-treated groups of all strains, but splenectomy inhibited the development of this type of lymphoma.
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PMID:Neoplasms in strains of splenectomized mice after a single 7,12-dimethylbenz[alpha]anthracene treatment. 17 27

Malonaldehyde (MA), a lipid peroxidation product derived from polyunsaturated fatty acids, is cytotoxic to a murine L5178Y lymphoma cell line cultured in vitro. Exposure of cells for 24 hours to as little as 20 microM MA produced detectable cytotoxicity as well as an increased number of mutants among survivors, using thymidine or methotrexate resistance as genetic markers. The induced mutation frequency, within the range of MA concentrations tested (10-100 microM), is dose-dependent. Significant division delay, which results in unbalanced growth, is also observed in MA-treated cells. It is suggested that MA crosslinks with DNA and mutagenizes cells through the error-prone repair system. In order to relate the degree of mutagenicity of MA in reference to other mutagenic agents in mammalian cells, the mutation frequency of the thymidine-resistance marker in L5178Y induced by X-irradiation is also presented. The significance of lipid peroxidation in relation to carcinogenesis and the various theories of aging will be briefly discussed.
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PMID:Mutagenicity and cytotoxicity of malonaldehyde in mammalian cells. 49 77

A case of gastric carcinoma, occurring 16 years after irradiation for gastric lymphoma, is presented. Factors which may have contributed to gastric carcinogenesis in this patient are discussed.
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PMID:Gastric carcinoma 16 years after gastric lymphoma irradiation. 58 Jan 64

Benz[a]anthracene and the five metabolically possible trans-dihydrodiols of benz[a]anthracene were tested for carcinogenicity in newborn Swiss-Webster mice. Four hundred, 800, and 1600 nmoles hydrocarbon i.p. were sequentially injected on Days 1, 8, and 15 of life. The mice were killed at 22 weeks of age. Of the mice treated with trans-3,4-dihydroxy-3, 4-dihydrobenz[a]anthracene, 24% developed malignant lymphoma, whereas 4% of the animals treated with benz[a]anthracene had malignant lymphoma. None of the animals treated with the trans-1,2-dihydroxy-1,2-dihydrobenz[a]anthracene, trans-5,6-dihydroxy-5,6-dihydrobenz[a]anthracene, trans-8,9-dihydroxy-8,9-dihydrobenz[a]anthracene, or trans-10,11-dihydroxy-10,11-dihydrobenz[a]anthracene had malignant lymphoma. trans-3,4-Dihydroxy-3,4-dihydrobenz[a]anthracene caused about 35-fold more pulmonary adenomas than did benz[a]anthracene, whereas the trans-1,2-dihydroxy-1,2-dihydrobenz[a]anthracene, trans-5,6-dihydroxy-5,6-dihydrobenz[a]anthracene, trans-8,9-dihydroxy-8,9-dihydrobenz[a]anthracene, and trans-10, 11-dihydroxy-10,11-dihydrobenz[a]anthracene had little or no activity. The exceptionally high carcinogenicity of trans-3,4-dihydroxy-3,4-dihydrobenz[a]anthracene is consistent with the metabolism of this compound to either or both of the diastereomeric bay region 3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrobenz[a]anthracenes, and the data support the bay region theory of polycyclic hydrocarbon carcinogenesis.
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PMID:Exceptional carcinogenic activity of benz[a]anthracene 3,4-dihydrodiol in the newborn mouse and the bay region theory. 62 73

An increasing incidence of bladder neoplasms temporally associated with chemotherapy, usually cyclophosphamide, is being reported. These secondary primary bladder malignancies are characteristically found in two groups of patients: those with lymphoproliferative or myeloproliferative tumors, and those with immunosuppression after organ transplantation. A case of adenocarcinoma of the bladder associated with malignant lymphoma is reported, and the known cases of second primary bladder malignancies after cyclophosphamide therapy as reported in the literature are reviewed. Studies relating to the enhanced occurrence of second primary cancers in lymphoproliferative disorders are presented. The recognized urologic toxicities of cyclophosphamide, including cytopathologic changes in animals and humans, are discussed. The observed association between immunosuppression and second primary malignancies is explored, as supported by studies on congenital immunodeficiency in humans, viral oncogenesis in experimental animals, and neoplasia after organ transplantation. Possible mechanisms of carcinogenesis associated with cyclophosphamide are reviewed, including suppression of humoral and cell-mediated immune defense mechanisms, direct carcinogenesis, or cocarcinogenesis. A plea is made for the orderly reporting and careful documentation of bladder tumors in patients receiving cyclophosphamide. It is suggested that prospective studies in these patients and in patients receiving cyclophosphamide for nonmalignant disorders would be of value in assessing the culpability of cyclophosphamide as a carcinogen.
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PMID:Does cyclophosphamide induce bladder cancer? 67 98

Tumors in rats of the Nb strain, arising either spontaneously or after prolonged treatment with s.c. pellets of estrogen, were transplanted to establish whether hormone conditioning was required for their growth. Whereas all spontaneous tumors arising in males and many of those in females were autonomous on transplant, most of those arising in estrogenized rats continued to require hormones for growth after transplantation. The latter included carcinomas of the adrenal cortex, breast, pituitary ectopic tissue, ovary (thecomas), Leydig cells of testis, thymus, pancreas,salivary glands, oribital gland (fibroadenoma), liposarcoma, and lymphoma. Many of the tissues of origin of the tumors have not been considered to be under theinfluence of estrogens. A type of hormone-responsive tumor that was inhibited by estrogen and that grew only in normal rats is described. Ali estrogens tested, including estriol , were interchangeable in action. The incidence of the more common tumors of the adrenal, breast, and pituitary was very low in normal rats, but higher in females. All tumors were more common after estrogenization in both sexes, particularyly in older animals. The secretion of steroids and pitiutary hormones by many tumors led to obvious biological effects. Pituitary secretion led to severe lesions frequently associated with diseases in humans, but the signs of such diseases in the rat apparently were hormone dependent and disappeared if the tumor was removed. The overall results raised the possiblity that estrogens were not carcinogenic per se but stimulated the growth of previously altered cells and that, following their transplantation, this hormone requirement was retained. Irrespective of the mechanism of carcinogenesis, hormone-dependent tumor growth was not irreversible but was controlled in an unexpectedly wide spectrum of organs by exogenous estrogen. Host factors may play a major role in controlling the growth of many tumors and the ultimate course of the disease.
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PMID:Spontaneous and estrogen-produced tumors in Nb rats and their behavior after transplantation. 116 9

Urinary bladder cancers following prolonged cyclophosphamide therapy are being increasingly reported. We report a case of transitional cell carcinoma of the urinary bladder occurring 12 years after pulse intravenous therapy with cyclophosphamide for Hodgkin's disease. The mechanism of bladder carcinogenesis and the possible role of the uroprotector MESNA in preventing cyclophosphamide induced bladder cancer are discussed.
Leuk Lymphoma 1992 Dec
PMID:Urinary bladder cancer following cyclophosphamide therapy for Hodgkin's disease. 129 84

111 chemicals of known rodent carcinogenicity (49 carcinogens, 62 noncarcinogens), including many promoters of carcinogenesis, nongenotoxic carcinogens, hepatocarcinogens, and halogenated hydrocarbons, were selected for study. The chemicals were administered by gavage in two dose levels to female Sprague-Dawley rats. The effects of these 111 chemicals on 4 biochemical assays (hepatic DNA damage by alkaline elution (DD), hepatic ornithine decarboxylase activity (ODC), serum alanine aminotransferase activity (ALT), and hepatic cytochrome P-450 content (P450)) were determined. Composite parameters are defined as follows: CP = [ODC and P450), CT = [ALT and ODC), and TS = [DD or CP or CT]. The operational characteristics of TS for predicting rodent cancer were sensitivity 55%, specificity 87%, positive predictivity 77%, negative predictivity 71%, and concordance 73%. For these chemicals, the 73% concordance of this study was superior to the concordance obtained from published data from other laboratories on the Ames test (53%), structural alerts (SA) (46%), chromosome aberrations in Chinese hamster ovary cells (ABS) (48%), cell mutation in mouse lymphoma 15178Y cells (MOLY) (52%), and sister-chromatid exchange in Chinese hamster ovary cells (SCE) (60%). The 4 in vivo biochemical assays were complementary to each other. The composite parameter TS also shows complementarity to all 5 other predictors of rodent cancer examined in this paper. For example, the Ames test alone has a concordance of only 53%. In combination with TS, the concordance is increased to 62% (Ames or TS) or to 63% (Ames and TS). For the 67 chemicals with data available for SA, the concordance for predicting rodent carcinogenicity was 47% (for SA alone), 54% (for SA or TS), and 66% (for SA and TS). These biochemical assays will be useful: (1) to predict rodent carcinogenicity per se, (2) to 'confirm' the results of short-term mutagenicity tests by the high specificity mode of the biochemical assays (the specificity and positive predictivity are both 100%), and (3) to be a component of future complementary batteries of tests for predicting rodent carcinogenicity.
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PMID:Predictive assay for rodent carcinogenicity using in vivo biochemical parameters: operational characteristics and complementarity. 137 35

Recently in vitro assays of mutagenesis have been criticized as being poorly predictive of long-term in vivo rodent assays of carcinogenicity. Questions have also been raised concerning the relevance of rodent assays to human risk. In vitro assays using mammalian cells can detect most types of genetic lesions thought to be important in human malignant disease. Molecular and cytogenetic analyses of mutations induced by a variety of genotoxic compounds at the heterozygous thymidine kinase locus in mouse lymphoma cells indicate that this in vitro assay does indeed register the range of genetic lesions recently found in a wide variety of human tumors. The types and complexity of the induced lesions are reflected in mutant colony phenotype in a compound-specific fashion. These studies point to the use of appropriate in vitro mammalian mutagenesis assays as new model systems for dissecting the genetic lesions important in human carcinogenesis, and as a means of determining the potential for compounds to induce such lesions.
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PMID:In vitro mammalian mutagenesis as a model for genetic lesions in human cancer. 138 37

A mathematical model simulating lymphomagenesis based on the two-hit theory of carcinogenesis is presented by contrasting the biologic variables responsible for a high risk of developing Burkitt lymphoma (BL) in three immunosuppressed groups with that of nonendemic BL. In this model, the pro-B lymphocyte is considered to be the target for BL-specific translocations such as t(8;14). With repeated mitosis, the target cell pool expands in the high-risk individual, and, thereby, the opportunities for a spontaneous translocation to arise are increased. The chromosomal translocation endows the target cell with survival advantages, and, hence, lymphoma develops. Modeling results demonstrate that this increased cell proliferation is sufficient in accounting entirely for the increase in tumor prevalence. Preventing enhanced cellular proliferation by obviating immune deficiency and treating patients with agents that restore immunity or have antiviral and antiproliferative properties prior to conversion from polyclonal B-cell proliferation to monoclonal malignancy could obviate the development of BL.
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PMID:Cellular proliferation and genetic events involved in the genesis of Burkitt lymphoma (BL) in immune compromised patients. 145 49


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