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

The present study reports the modulatory influences of combined oral contraceptive formulations, Ovral (0.05 mg ethinylestradiol plus 0.5 mg norgestrel per pill) and Noracycline (0.05 mg ethinylestradiol plus 0.1 mg lynestrenol per pill), on methylcholanthrene (MCA)-induced carcinogenesis in the uterine cervix of Swiss albino mouse. Placement of cotton thread impregnated with beeswax containing approximately 300 micrograms of MCA yielded cervical tumors in 0.0%, 8.6% and 26% animals, respectively, in 30, 60 and 90 days. Concomitant treatments with doses D1 (1/2000th of a pill), D2 (1/200th of a pill) and D3 (1/20th of a pill) of Ovral yielded cervical tumors in 0.0%, 0.0% and 4.5% mice at 30 days, 0.0%, 6.2% and 10% mice at 60 days and in 3.3% (P less than 0.05), 3.4% (P less than 0.05) and 47% mice at 90 days, respectively. Likewise, concomitant treatments with doses D1 (1/2000th of a pill), D2 (1/200th of a pill) and D3 (1/20th of a pill) of Noracycline yielded cervical tumors in 0.0%, 0.0%, 16.6% mice at 30 days, 4%, 3.7% and 54% (P less than 0.05) mice at 60 days and 3.2% (P less than 0.05), 20% and 63% (P less than 0.05) of mice at 90 days, respectively. Both Ovral and Noracycline displayed biphasic action on MCA-induced cervical carcinogenesis in mice. At lower dose levels (D1 and D2), they were inhibitory while at the higher dose level (D3) they were augmentatory in their actions. Both pills also significantly enhanced the incidence of cervical hyperplasia.
 ...
PMID:Modulatory influence of oral contraceptive pills Ovral and Noracycline on 3-methylcholanthrene-induced carcinogenesis in the uterine cervix of mouse. 164 61

N-Acyl dehydroalanines have shown free radical scavenging activity. They react with and scavenge mainly oxygen-derived free radicals such as the superoxide anion (O2-.) and the hydroxyl radical (HO.). Ortho-methoxyphenylacetyl dehydroalanine (AD-20) protects total-body irradiated mice against the toxicity induced by X-rays when delivered as a single dose of 700 rads in a short period of time. This degree of protection was of the same order of magnitude as that obtained with the aminothiol S-2-(3-aminopropylamino)-ethylphosphorothioic acid (WR-2721). The radioprotection of AD-20 is extended to all other doses of X-rays tested (from 600 to 800 rads). Furthermore, AD-20 inhibits the development of thymic lymphomas in C57Bl/Ka mice undergoing a leukaemogenic course of irradiation (4 x 175 rads applied at weekly intervals). We postulate that AD-20 may act as a radioprotector and anticarcinogenic agent, most probably by inactivating the oxygen-derived free radicals formed during water radiolysis.
Carcinogenesis 1989 Sep
PMID:N-acyl dehydroalanines protect from radiation toxicity and inhibit radiation carcinogenesis in mice. 254 51

The present study examines the modulatory influence of the combined oral contraceptive pill, Ovral (0.05 mg ethynylestradiol plus 0.25 mg levonorgestrel per pill) on methylcholanthrene (MCA)-induced carcinogenesis in the uterus of Swiss albino mouse. Placement of cotton thread impregnated with beeswax containing approximately 600 micrograms of MCA, yielded endometrial squamous cell carcinomas in 53.33% animals in 90 days. Concomitant treatments with doses D1 (1/200th of a pill) and D2 (1/200th of a pill) of Ovral yielded endometrial squamous cell carcinomas in 6.23 and 0% of animals in 90 days (p < 0.05; p < 0.005) respectively. Ovral did not seem to increase the incidence of uterine hyperplasia.
 ...
PMID:Modulatory influence of the oral contraceptive pill, Ovral, on 3-methylcholanthrene-induced carcinogenesis in the uterus of mouse. 780 Mar 39

In the last few years research efforts have succeeded in detectury the genetic background of several hereditary hearing disorders by molecular biological methods. The genetic code was been decoded for Neurofibromatosis types 1 and 2, as well as for such X-linked diseases as Alport's syndrome or Norrie's disease. Besides the classic genetic tools as chromosomal analysis, molecular biological techniques and methods have become important clinically for the ENT-specialist. In the present review we show the principles and applications of DNA-and RNA-analysis with hybridization techniques in Southern- and Northern-blot techniques, as well as in-situ hybridization and polymerase chain reaction (PCR). These molecular biological techniques will help improve the detection and analysis of hereditary inner ear disorders, but also be able to study in greater detail tumor carcinogenesis and mutagenesis. The various techniques are explained and the applications are demonstrated.
 ...
PMID:[Perspectives of molecular genetics of hearing disorders]. 846 17

In the upper aerodigestive tract, carcinogenesis in squamous cell mucosa is characterized by a tendency to field carcinogenesis leading to multicentricity of lesions and synchronous or metachronous multiple tumoral lesions, namely multifocality. During pretherapy broncho-esophagoscopy carried out on ENT-cancer patients, the rate of synchronous second primary cancer is 24%. In 85% of the cases, these second primaries are detected at an early stage (in situ, microinvasive or submucosal carcinoma) and do not give rise to symptoms. Early diagnosis of cancer of the upper aerodigestive tract is possible provided that high risk patients are recognized and screening endoscopy of the whole mucosa is performed in every high risk patient. On the other hand, squamous cell carcinoma and adenocarcinoma may occur with increased frequency in patients with esophageal lesions such as achalasia, caustic stenosis and Barrett's esophagus. The premalignant potential of these three entities is discussed.
 ...
PMID:[Precancerous conditions of the esophagus]. 851 40

While the accumulation of genetic changes in a somatic cell is considered essential for the genesis of a cancer, it has become clear that not all carcinogens are genotoxic, suggesting that some carcinogens indirectly participate in the generation of genetic changes during carcinogenesis. A European project funded by the European Community was thus conceived to study mechanisms of nongenotoxic aspects of carcinogenesis. Two main strategical approaches were adapted: (i) to study whether and how Syrian hamster embryo (SHE), Syrian hamster dermal (SHD) and BALB/c 3T3 cell transformation systems simulate in vivo carcinogenesis, and to examine whether they can detect nongenotoxic carcinogens; (ii) to study, refine and validate mechanisms-based end-points for detection of nongenotoxic carcinogens. For mechanisms-based research, the proposed end-points included gap junctional intercellular communication (GJIC) inhibition, altered expression of critical genes, immortalization and aberrant cell proliferation. We also selected model compounds commonly usable for various endpoints. Our major results can be summarized as follows: (1) SHE and BALB/c 3T3 transformation systems reflect both genotoxic and nongenotoxic carcinogenic events; they detect not only genotoxic but also many although not all, nongenotoxic carcinogens. This is further supported by the fact that both genotoxic and nongenotoxic carcinogens were able to immortalize SHD cells. (2) Many nongenotoxic carcinogens, although not all, inhibit GJIC in vitro as well as in vivo. Mechanistic studies suggest an important role of blocked GJIC in carcinogenesis and that different mechanisms are involved in inhibition of the communication by different agents used. However, inhibition of GJIC is not a prerequisite for the enhancement (or induction) of transformation of SHE or BALB/c 3T3 cells. (3) Among compounds examined, there was a good correlation between induction of micronuclei and cell transformation in SHE cells while no such correlation was found between the induction of cell transformation and ornithine decarboxylase activity. (4) Two transgenic mouse mutation assays (lacI and lacZ) were established and validated. The genotoxin dimethylnitrosamine was shown to be mutagenic to the liver in both assays. Ortho-anisidine, a bladder-specific carcinogen that was inactive in standard rodent genetic toxicity assays was uniquely mutagenic to the bladder of the transgenic mice. The peroxisome proliferator methyl clofenipate was established as nonmutagenic to the liver of both transgenic mice. That eliminated DNA damage as a cause of the liver tumours produced by this chemical and weakened the idea that induced cell division leads to mutation induction. (5) With an in vitro DNA replication model, it was found that DNA damage induced by genotoxic agents can be responsible for inhibition of DNA replication, while certain nongenotoxic agents such as phorbol esters increase DNA replication. (6) An attempt to use structure-activity relationship for subfamilies of nongenotoxic carcinogens, e.g., receptor-mediated carcinogens, has been initiated with some promising results. Our results support the idea that there are multiple nongenotoxic mechanisms in carcinogenesis, and that working hypothesis-oriented approaches are encouraged rather than simple screening of chemicals in developing test systems for the detection of nongenotoxic carcinogens.
 ...
PMID:Nongenotoxic carcinogens: development of detection methods based on mechanisms: a European project. 869 92

As retrovirus-induced neoplasms of the respiratory epithelium of sheep and goats, OPC and ENT rank as economically important diseases in many countries of the world. They are also important as models of retroviral carcinogenesis of the secretory epithelium of the respiratory system. Control of both diseases is dependent on development and application of sensitive and specific assays for identification of carrier animals infected with the causative agents of these diseases. Recent progress in characterization of type D/B retroviruses associated with the diseases and development of new reagents for the immunologic or molecular detection of antiviral antibodies, viral proteins, or viral nucleic acids bodes well for improved control or prevention of these diseases.
 ...
PMID:Retrovirus-associated neoplasms of the respiratory system of sheep and goats. Ovine pulmonary carcinoma and enzootic nasal tumor. 907 46

Ortho-phenylphenol (OPP) and sodium ortho-phenylphenate (NaOPP) are pesticides used commercially in the food industry that have been shown to be carcinogenic to rat urothelium. Dietary administration of 1.25% OPP or 2.0% NaOPP caused increased incidences of urothelial hyperplasia and eventually caused tumors in male F344 rats, with NaOPP apparently having a more potent effect. In other studies, various sodium salts such as saccharin and ascorbate enhanced bladder carcinogenesis, although the acid forms of these salts did not. In studies with high dietary doses of these sodium salts, an amorphous precipitate was produced in the urine; precipitate formation was pH dependent. In previous experiments in which high doses of OPP were fed for up to 17 weeks, severe hyperplasia of the urothelium was produced, but without the formation of an urinary amorphous precipitate, calculi, or abnormal microcrystalluria. In addition, we found no evidence of OPP-DNA adduct formation in the urothelium. The present study was conducted to determine if feeding NaOPP * 4 H(2)0 to male F344 rats as 2.0% of the diet resulted in the formation of an amorphous precipitate in the urine, and if NaOPP caused an increased mineral concentration in the urine and/or kidneys. NaOPP administration produced a higher urinary pH than did OPP fed as 1.25% of the diet. Neither amorphous precipitate nor other solids were observed in the urine of the OPP or NaOPP-treated rats, and urinary calcium concentrations in the treated groups were similar to control. OPP and NaOPP had similar proliferative effects on rat urothelium after 10 weeks of treatment by light microscopy, scanning electron microscopy (SEM), and bromodeoxyuridine (BrdU) labeling indices. The results of this study indicate that formation of abnormal urinary solids is not part of the mechanism by which OPP or NaOPP exert their effects on the rat bladder epithelium.
 ...
PMID:Dietary effects of ortho-phenylphenol and sodium ortho-phenylphenate on rat urothelium. 1115 28

Tetrachloroethylene is used primarily as a dry cleaning agent, an industrial solvent for fats, oils, tars, rubber, and gums, and a metal degreasing agent. Tetrachloroethylene had antihelminthic uses, particularly for hookworms (1.6-8 g/60 kg), and was formerly used in combination with some grain protectants and fumigants. Toxicology and carcinogenesis studies of tetrachloroethylene (99.9% pure) were conducted by inhalation exposure of groups of 50 male and 50 female F344/N rats and B6C3F1 mice 6 hours per day, 5 days per week, for 103 weeks. The exposure concentrations used (0, 200, or 400 ppm for rats and 0, 100, or 200 ppm for mice) were selected on the basis of results from 13-week inhalation studies in which groups of 10 rats and 10 mice of each sex were exposed to tetrachloroethylene at 100-1,600 ppm for 6 hours per day, 5 days per week. During the 13-week studies, 1,600 ppm tetrachloroethylene was lethal to 20%-70% of the rats and mice and reduced the final body weights of survivors. In rats, tetrachloroethylene at 200-800 ppm caused minimal to mild hepatic congestion. In dosed male and female mice, minimal to mild hepatic leukocytic infiltration, centrilobular necrosis, bile stasis (400-1,600 ppm), and mitotic alteration (200-1,600 ppm) were produced. Tetrachloroethylene exposure also caused minimal renal tubular cell karyomegaly in mice at concentrations as low as 200 ppm. During the 2-year studies, exposure to tetrachloroethylene did not consistently affect body weight gains in either rats or mice. Exposure at 400 ppm tetrachloroethylene reduced the survival of male rats (control, 23/50; low dose, 20/50; high dose, 12/50). This reduced survival may have been related to an increased incidence of mononuclear cell leukemia. Tetrachloroethylene at both exposure concentrations reduced the survival of male mice (46/50; 25/50; 32/50), whereas exposure at 200 ppm reduced female mouse survival (36/50; 31/50; 19/50). Early deaths in mice may have been related to the development of hepatocellular carcinomas. Both concentrations of tetrachloroethylene were associated with increased incidences of mononuclear cell leukemia in male rats (28/50; 37/50; 37/50). In female rats, tetrachloroethylene increased the incidence of leukemia (18/50; 30/50; 29/50) and decreased the time to occurrence of the disease. Tetrachloroethylene produced renal tubular cell karyomegaly in male and female rats, renal tubular cell hyperplasia in male rats, and renal tubular cell adenomas or adenocarcinomas (combined) in male rats (1/49; 3/49; 4/50). The incidence of the renal tubular cell tumors was not statistically significant; these uncommon tumors have been consistently found at low incidences in male rats in other 2-year studies of chlorinated ethanes and ethylenes. One low dose male rat had a kidney lipoma, and another had a nephroblastoma. Four high dose male and two high dose female rats had gliomas of the brain, whereas one control male and one control female had this tumor. In male and female mice, tetrachloroethylene caused dose-related increases in the incidences of hepatocellular neoplasms. In males, tetrachloroethylene at 200 ppm increased the incidence of hepatocellular adenomas (11/49; 8/49; 18/50) and at both concentrations increased the incidence of hepatocellular carcinomas (7/49; 25/49; 26/50). In female mice, tetrachloroethylene at both concentrations increased the incidences of hepatocellular carcinomas (1/48; 13/50; 36/50). Tetrachloroethylene also produced renal tubular cell karyomegaly in both sexes of mice, and one low dose male mouse had a tubular cell adenocarcinoma. In these inhalation studies, there were no neoplastic changes in the respiratory tracts of either species, but there was an increase in the incidence of squamous metaplasia in the nasal cavities in dosed male rats (0/50; 5/50; 5/50). Tetrachloroethylene was not mutagenic in Salmonella typhimurium strains TA98, TA100, TA1535, or TA1537 in the presence or absence of male Syrian hamster or male Sprague-Dawley rat liver S9. Tetrachloroethylene was not mutagenic in was not mutagenic in L5178Y/TK&plusmn; mouse lymphoma cells with or without metabolic activation and did not induce sex-linked recessive lethal mutations in Drosophila melanogaster. Tetrachloroethylene did not induce sister-chromatid exchanges or chromosomal aberrations in Chinese hamster ovary cells in the presence or absence of metabolic activation. An audit of the experimental data was conducted for these 2-year studies on tetrachloroethylene. No data discrepancies were found that influenced the final interpretations. Under the conditions of these 2-year inhalation studies, there was clear evidence of carcinogenicity of tetrachloroethylene for male F344/N rats as shown by an increased incidence of mononuclear cell leukemia and uncommon renal tubular cell neoplasms. There was some evidence of carcinogenicity of tetrachloroethylene for female F344/N rats as shown by increased incidences of mononuclear cell leukemia. There was clear evidence of carcinogenicity for B6C3F1 mice as shown by increased incidences of both hepatocellular adenomas and carcinomas in males and of hepatocellular carcinomas in females. Synonyms: carbon bichloride; carbon dichloride; ethylene tetrachloride; per; perc; perchlor; perchlorethylene; perchloroethylene; perk; tetrachlorethylene; 1,1,2,2-tetrachloroethylene Trade names: Ankilostin; Antisal 1; Dee-Solv; Didakene; Dow-Per; ENT 1860; Fedel-Un; Nema; Perclene; Percosolv; Perklone; PerSec; Tetlen; Tetracap; Tetraleno; Tetravec; Tetroguer; Tetropil
 ...
PMID:NTP Toxicology and Carcinogenesis Studies of Tetrachloroethylene (Perchloroethylene) (CAS No. 127-18-4) in F344/N Rats and B6C3F1 Mice (Inhalation Studies). 1274 18

Association of infection with papillomavirus and dysplasia of the cervix uteri has been firmly established. There are only few cervical cancers where no HPV DNA is detectable. The mechanism of epithelial cell immortalization by interaction with tumour suppressor genes p53 and pRb by viral oncogenes E6 and E7 is elucidated. Progression of the HPV infected cell to a malignant phenotype involves further modification of host gene expression and/or mutations. The appearance of chromosomal aberrations can lead to mutational inactivation or loss of tumour suppressor genes (TSG), activation and amplification of oncogenes, with importance for the process of carcinogenesis. Oncogene amplification, with exception of few reports, seems not to be a major mechanism in cervical carcinogenesis. In contrast, cytogenetic and loss of heterozygosity (LOH) results from CIN and invasive cancer demonstrate alterations at specific chromosomal regions, pointing at localisation of TSG. Genetic alterations at chromosomes 3p, 6p, 1lq were frequently found early in tumour development Primary invasive carcinoma showed additional allelic losses at chromosome arms 6q, 17p and 18q. Useful biological diagnostic and prognostic markers for high-risk HPV infection and malignant progression may be p16NK4 p27Kip, and NET-I/C4.8. Putative senescence genes relevant for HPV-induced carcinogenesis are localized on chromosomes 2, 4 and 10. Genes for Telomerase suppression are presumably located on chromosomes 3, 4 and 6. Natural immune responses to HPV infection exist Therefore, immune therapy is an attractive possibility for prevention and therapy of HPV infection. To date, vaccine development has reached clinical evaluation. Prophylaxis aims at the induction of virus neutralizing antibodies to capsid proteins. Virus-like particle vaccines are currently tested in clinical trials. Due to the long lag period between infection and clinical manifestation trials will take a long time until conclusive results are obtained. Mandatory expression of viral and perhaps certain cellular genes in infected epithelial and tumour cells offers targets for therapeutic approaches. Since most dysplasia clears spontaneously the viral infection is immunogenic to some extent. However, in some individuals the immune response has to be stimulated by vaccination in order to be effective. Several strategies are being tested in clinical trials and others are in preclinical development The task will be to circumvent immunosuppressive features of the HPV infected cells.
 ...
PMID:HPV induced cervical carcinogenesis: molecular basis and vaccine development. 1279 44


1 2 Next >>