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)

In order to replace antiknock leaded derivatives in gasoline, legislations were enacted in the United States and other countries to find safer additives and to reduce CO, O3, and volatile organic compounds (VOCs) in non-attainment areas. Oxygenates commonly used include various alcohols and aliphatic ethers. Methyl tert-butyl ether (MTBE) is the most widely used and studied ether oxygenate and is added to gasoline at concentrations up to 15% by volume. Inhalation of fumes while fueling automobiles is the main source of human exposure to MTBE. Humans are also exposed when drinking water contaminated with MTBE. Epidemiological, clinical, animal, metabolic and kinetic studies have been carried out to address human health risks resulting from exposure to MTBE. MTBE is an animal carcinogen, but its human carcinogenic potential remains unclear. Because MTBE functions as a non-traditional genotoxicant, several mechanisms were suggested to explain its mode of action, such as, functioning as a cytotoxic as opposed to a mitogenic agent; involvement of hormonal mechanisms; or operating as a promoter instead of being a complete carcinogen. Some studies suggested that carcinogenicity of MTBE might be due to its two main metabolites, formaldehyde or tributanol. A role for DNA repair in MTBE carcinogenesis was recently unveiled, which explains some, but not all effects. The totality of the evidence shows that, for the majority of the non-occupationally exposed human population, MTBE is unlikely to produce lasting adverse health effects, and may in some cases improve health by reducing the composition of emitted harmful VOCs and other substances. A small segment of the population (e.g. asthmatic children, the elderly, and those with immunodeficiency) may be at increased risk for toxicity. However, no studies have been conducted to investigate this hypothesis. Concern over ground and surface water contamination caused by persistent MTBE has lead the Environmental Protection Agency (EPA) to proposed reducing or eliminating its use as a gasoline additive. The major potential alternatives to MTBE are other forms of ethers such as ethyl tert-butyl ether (ETBE) or tert-amyl methyl ether (TAME), and alcohols such as ethanol. More definitive studies are needed to understand the mechanism(s) by which aliphatic ethers may pose health and environmental impacts. The switch from MTBE to ethanol is not without problems. Ethanol costs more to produce, poses challenges to the gasoline distribution system, extends the spread of hydrocarbons through ground water in gasoline plumes, and in the short-term is unlikely to be available in sufficient quantity. Moreover, its metabolite acetaldehyde is a possible carcinogen that undergoes a photochemical reaction in the atmosphere to produce the respiratory irritant peroxylacetate nitrate (PAN). Congress is addressing whether the Clean Air Act Amendments (CAA) provisions concerning reformulated gasoline (RFG) should be modified to allow refineries to discontinue or lessen the use of oxygenates.
 ...
PMID:Toxicology and human health effects following exposure to oxygenated or reformulated gasoline. 1164 Oct 38

Hepatitis B virus (HBV) is the most meaningful risk factor in chronic hepatitis, cirrhosis and primary hepatocellular carcinoma (PHC). The hepatitis B virus X protein (HBxAg) is a multifunctional protein with many important functions in hepatocellular carcinogenesis. A monoclonal anti-HBxAg antibody was developed in our laboratory and characterized by different methods. Using this antibody HBxAg was detected in formaldehyde fixed paraffin embedded tissue sections of 72 liver biopsies from patients with acute hepatitis, chronic hepatitis, cirrhosis and primary hepatocellular carcinoma. The co-expression of hepatitis B surface antigen (HBsAg), hepatitis B core antigen (HBcAg) and HBxAg was compared. The histological and cytological localization of the detected HBxAg showed a characteristic distribution in different stages of HBV infection. Strong and diffuse nuclear reaction was detected in PHC cases in contrast to the focal, cytoplasmic and nuclear labeling in the acute and chronic B hepatitis cases. Our antibody seems to be a suitable prognostic marker for routine pathohistological diagnosis and for comparative pathological and epidemiological research on the development of PHC.
 ...
PMID:Immunohistochemical assessment and prognostic value of hepatitis B virus X protein in chronic hepatitis and primary hepatocellular carcinomas using anti-HBxAg monoclonal antibody. 1169 43

Enzymes involved in various protective and metabolic processes of carbonyl compounds were analysed utilising a micro-array method in a three-stage in vitro model for oral carcinogenesis involving cultured normal, immortalised and malignant human oral keratinocytes. A complete transcript profiling of identified carbonyl-metabolising enzymes belonging to the ADH, ALDH, SDR and AKR families is presented. Expression of 17 transcripts was detected in normal, 14 in immortalized and 19 in malignant keratinocytes of a total of 12,500 genes spotted on the micro-array chip. For the detected transcripts, about half were changed by cell transformation, and for the various enzyme families, differences in expression patterns were observed. The detected AKR transcripts displayed a conserved pattern of expression, indicating a requirement for the keratinocyte phenotype, while most of the detected SDRs displayed changed expression at the various stages of malignancy. The importance of multiple experiments in using a microarray technique for reliable results is underlined and, finally, the strength of the method in detecting co-expressed enzymes in metabolic pathways is exemplified by the detection of the formaldehyde-scavenging pathway enzymes and the polyol pathway enzymes.
 ...
PMID:Micro-array chip analysis of carbonyl-metabolising enzymes in normal, immortalised and malignant human oral keratinocytes. 1170 98

C.I. Direct Blue 218 is a copper chelated dye used for cellulose, acetate, nylon, silk, wool, tissue, papers, and textile goods with a urea-formaldehyde finish. C.I. Direct Blue 218 is one of five chemicals/dyes that are part of the National Toxicology Program's Benzidine Dye Initiative, established to determine the toxicity and carcinogenicity of representative benzidine congeners, congener-derived dyes, and benzidine-derived dyes. Industrial grade C.I. Direct Blue 218 was selected for study because of its widespread use. Because of the high salt content, the dye was desalted prior to use. Toxicology and carcinogenesis studies were conducted by administering C.I. Direct Blue 218 in feed to groups of male and female F344/N rats and B6C3F1 mice for 14 days, 13 weeks, and 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and Drosophila melanogaster. 14-DAY STUDY IN RATS: Groups of five male and five female F344/N rats were fed diets containing 0, 1,000, 3,000, 7,000, 15,000, or 30,000 ppm C.I. Direct Blue 218. All rats survived until the end of the study. Rats receiving 30,000 ppm lost weight, and the mean body weight gain of males receiving 15,000 ppm was significantly lower than that of the controls. Feed consumption by rats receiving 30,000 ppm was lower than that by the controls. Decreased organ weights at the 30,000 ppm level were related to the decreased body weights at this exposure level. 14-DAY STUDY IN MICE: Groups of five male and five female mice were fed diets containing 0, 1,000, 3,000, 7,000, 15,000, or 30,000 ppm C.I. Direct Blue 218. All mice survived until the end of the study. The final mean body weight of males receiving 30,000 ppm was 25% lower than that of controls and that of 30,000 ppm females was 20% lower than that of controls. Feed consumption by exposed and control groups was similar except for the 15,000 and 30,000 ppm groups. Feed spillage, due to reduced palatability, precluded the accurate determination of feed consumption by these two groups. Male and female mice receiving 30,000 ppm appeared hyperactive and emaciated during the last week of the study. Decreased organ weights were noted at 30,000 ppm and were attributed to the decreased mean body weights at this exposure level. 13-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were fed diets containing 0, 3,000, 10,000, or 20,000 ppm C.I. Direct Blue 218. All male and female rats survived until the end of the study. Rats exposed to 3,000,10,000, or 20,000 ppm C.I. Direct Blue 218 received approximate daily doses of 200, 600 or 1,300 mg dye/kg body weight (males) and 200, 800, or 1,400 mg/kg (females). The final mean body weight of male rats receiving 20,000 ppm was 24% lower than that of the controls and the final mean body weight of female rats receiving 20,000 ppm was 15% lower than that of the controls. Feed consumption by exposed and control groups was similar except in the 20,000 ppm groups where feed spillage was noted. Absolute and relative kidney weights of rats receiving 10,000 or 20,000 ppm were significantly greater than those of controls. Significantly decreased organ weights were noted, particularly in the 20,000 ppm groups, and were attributed to the lower mean body weights at this exposure level. The hematocrit, hemoglobin, mean erythrocyte volume, and mean erythrocyte hemoglobin values in male and female rats receiving 10,000 and 20,000 ppm were significantly lower than those of controls. Serum levels of alanine aminotransferase and sorbitol dehydrogenase in male and female rats receiving 20,000 ppm were significantly higher than those of controls, which is consistent with hepatocellular injury. Male rats receiving 10,000 ppm and male and female rats receiving 20,000 ppm had hepatic lesions consisting of intracytoplasmic pigment in periportal Kupffer cells, minimal to mild individual hepatocyte necrosis, increased numbers of binucleated and multinucleated hepatocytes, and minimal bile duct hyperplasia. Male and female rats receiving 20,000 ppm had ys receiving 20,000 ppm had yellow-green pigment within the cytoplasm of proximal convoluted tubules of the kidney. Microconcretions of mineral were observed along the corticomedullary junction of the kidney in most female rats, but the numbers of microconcretions in kidney sections were increased in females that received 20,000 ppm. 13-WEEK STUDY IN MICE: Groups of 10 male and 10 female B6C3F1 mice were fed diets containing 0, 3,000, 10,000, or 20,000 ppm C.I. Direct Blue 218. There were no deaths attributed to C.I. Direct Blue 218. Mice exposed to 3,000, 10,000, or 20,000 ppm C.I. Direct Blue 218 received approximate daily doses of 400, 1,500, or 3,600 mg dye/kg body weight (males) and 400, 1,800, or 4,000 mg/kg (females). The final mean body weight of males that received 20,000 ppm was 24% lower than that of the controls, and the final mean body weight of females that received 20,000 ppm was 14% lower than that of controls. Feed consumption by exposed mice was similar to that by controls except in the 20,000 ppm groups where feed spillage was noted. Significant differences in organ weights were noted at 20,000 ppm which were attributed primarily to the lower mean body weights in these exposure groups. The hematocrit, hemoglobin, mean erythrocyte volume, and mean erythrocyte volume, and mean erythrocyte hemoglobin values were significantly lower in males and females receiving 10,000 and 20,000 ppm. Serum levels of alanine aminotransferase and sorbitol dehydrogenase in male and female mice receiving 10,000 and 20,000 ppm were significantly higher than those of controls, indicating hepatic injury. Male and female mice receiving 20,000 ppm had hepatic lesions consisting of centrilobular hepatocyte hypertrophy and karyomegaly, multifocal individual hepatocyte necrosis, oval cell proliferation, and periportal Kupffer cells with intracytoplasmic pigment. Males and females receiving 20,000 ppm also had increased numbers of pigmented macrophages within the red pulp of the spleen. 2-YEAR STUDY IN RATS: The doses selected for the 2-year study of C.I. Direct Blue 218 were based on the lower final mean body weights and the occurrence of hepatic lesions in the 20,000 ppm groups in the 13-week study. Groups of 60 male and 60 female rats were fed diets containing 0, 1,000, 3,000, or 10,000 ppm C.I. Direct Blue 218 for 103 weeks. Nine or 10 rats from each group were evaluated after 15 months. Survival, Body Weights, Feed and Compound Consumption, and Clinical Findings: Survival of female rats receiving 10,000 ppm was slightly, but not significantly, lower than that of the controls. Mean body weights of male and female rats in the 10,000 ppm groups were approximately 5% to 14% lower than those of the controls after week 15, and the final mean body weights of male and female rats at this level were 11% and 9% lower than those of the controls, respectively. Feed consumption by exposed male and female rats was similar to that by the controls and was estimated to deliver daily doses of 40, 120, and 440 mg dye/kg body weight to males and 50, 140, and 470 mg/kg to females. No chemical-related clinical signs of toxicity were noted. Hematology and Clinical Chemistry: The hematocrit, hemoglobin, mean erythrocyte volume, and mean erythrocyte hemoglobin values in 10,000 ppm female rats were significantly lower than those of controls, while in males only the mean erythrocyte hemoglobin value was significantly lower. Serum levels of alanine aminotransferase and sorbitol dehydrogenase in male and female rats receiving 10,000 ppm were significantly higher than those of the controls at the 15-month interim evaluation. Pathology Findings: Squamous cell papillomas of the oral mucosa (pharynx) occurred in five males receiving 10,000 ppm but not in the lower exposure groups or in controls. A squamous cell carcinoma occurred in one 10,000 ppm male and a benign basosquamous tumor was observed in another. The incidence of oral mucosal neoplasms in the 10,000 ppm males was significantly greater than that in controls and exceeded the range observed in untreated historical controls (lO/l,253, 0.8%; range 0%-4%). These neoplasms were considered chemical related. Administration of C.I. Direct Blue 218 to rats produced significantly increased incidences of forestomach basal cell hyperplasia in males receiving 3,000 or 10,000 ppm (0 ppm, 0/50; 1,000 ppm, 2/50; 3,000 ppm, 10/50;10,000 ppm, 19/50) and in females receiving 10,000 ppm (1/50, 1/49, 5/50, 11/49). Further, there were marginal increased incidences of focal squamous hyperplasia in the 3,000 and 10,000 ppm males (1/50,1/50, 6/50, 4/50). Squamous cell papillomas of the forestomach were seen in two 3,000 ppm males and in one 10,000 ppm male; no papillomas were observed in the controls. A squamous cell carcinoma was also seen in one 3,000 ppm male. Because of the uncommon occurrence of forestomach neoplasms in untreated control male rats (4/1,253, 0.3%; range 0%-2%) and the slight increase in the incidence of focal hyperplasia, these neoplasms may have been chemical related. The incidence of uterine endometrial stromal polyps in each exposed group of female rats was significantly greater than that of the controls (1/50,12/50,10/50, 10/50). Because the incidences in the exposed groups did not increase in a dose-related manner and the incidence in the controls was unusually low (historical incidence: 205/1,251,16.4%; range 2%-30%), the higher incidence of stromal polyps in the exposed groups was not considered chemical related. 2-YEAR STUDY IN MICE: The dose selection for the 2-year study was based on the lower final mean body weights and the liver lesions observed at the 20,000 ppm level in the 13-week study. Groups of 60 male and 60 female mice were fed diets containing 0, 1,000, 3,000, or 10,000 ppm C.I. Direct Blue 218 for 103 weeks. Nine or 10 mice from each exposure group were evaluated after 15 months. Survival, Body Weights, Feed and Compound Consumption, and Clinical Findings: Survival of exposed male and female mice was similar to that of the controls. Mean body weights of male and female mice receiving 10,000 ppm were 10% to 29% lower than those of the controls during most of the study, and the final mean body weights in these groups were 19% lower than that of the controls for males and 27% lower than that of the controls for females. Feed consumption by exposed mice was similar to that by controls and the diets were estimated to deliver daily doses of approximately 120, 360, and 1,520 mg of dye/kg body weight to males and 140, 470, and 2,050 mg/kg to females. No chemical-related clinical signs of toxicity were noted. Hematology and Clinical Chemistry: Hematocrit, hemoglobin, and mean erythrocyte volume values in males and females receiving 10,000 ppm were significantly lower than those of the controls. Serum levels of alanine aminotransferase and/or sorbitol dehydrogenase values in male and female mice that received 10,000 ppm were significantly higher than those of controls, which is consistent with hepatocellular damage. Pathology Findings: The administration of C.I. Direct Blue 218 to mice produced significantly increased incidences of hepatocellular adenoma (0 ppm, 16/50; 1,000 ppm, 19/50; 3,000 ppm, 17/50; 10,000 ppm, 40/50) and hepatocellular carcinoma (7/50, 3/50, 8/50,17/50) in males receiving 10,000 ppm, and a significantly increased incidence of hepatocellular adenoma in females receiving 3,000 or 10,000 ppm (7/49, 12/50, 17/49, 41/49). In females that received 10,000 ppm, the incidence of hepatocellular carcinoma was marginally increased. Consistent with these findings, the incidence of hepatocellular foci of cytologic alteration, a preneoplastic lesion, was also increased in males and females in the 10,000 ppm groups. The increased incidences of hepatocellular foci, adenomas, and carcinomas were considered chemical related. Uncommon renal tubule neoplasms also occurred at low incidences in male mice receiving C.I. Direct Blue 218, but not in controls. Renal tubule adenomas were seen in two males receiving 1,000 ppm, one male receiving 3,000 ppm, and one male receiving 10,000 ppm. A renal tubule carcinoma was also seen in one male that received 1,000 ppm. Because renal tubule neoplasms are uncommon in male mice (4/1,366, 0.3%; range 0%-2%), these neoplasms may have been chemical related. Carcinomas of the small intestine occurred in four male mice receiving 10,000 ppm. One was observed at the 15-month interim evaluation, while the other three were observed in mice at the end of the study. One control male mouse also had a carcinoma of the small intestine. Because of the uncommon occurrence of small intestine neoplasms in untreated male mice (12/1,374, 0.9%; range 0%-4%), the slightly higher incidence of these neoplasms in males receiving 10,000 ppm may have been chemical related. Carcinomas of the small intestine also occurred in one 3,000 ppm and one 10,000 ppm female, but the low incidences precluded drawing an association with chemical administration. GENETIC TOXICOLOGY: C.I Direct Blue 218 was not mutagenic in Salmonella typhimurium strains TA98, TA100, TA1535, or TA1537 tested with and without exogenous metabolic activation (S9). It was also tested in a modified Salmonella test protocol which employed reductive metabolism supplied by flavin mononucleotide or rat cecal bacteria, followed by oxidative metabolism; results of this test using strain TA1538 were also negative. C.I. Direct Blue 218 induced a small but significant increase in sister chromatid exchanges in Chinese hamster ovary cells at the highest dose tested without S9. No increase in chromosomal aberrations were observed in Chinese hamster ovary cells with or without S9. C.I. Direct Blue 218 did not induce sex-linked recessive lethal mutations in germ cells of male Drosophila melanogaster. CONCLUSIONS: Under the conditions of these 2-year feed studies, there was some evidence of carcinogenic activity of C.I. Direct Blue 218 in male F344/N rats based on the occurrence of pharyngeal neoplasms. Squamous cell neoplasms of the forestomach may have been chemical related. There was no evidence of carcinogenic activity of C.I Direct Blue 218 in female F344/N rats given 1,000, 3,000, or 10,000 ppm. There was clear evidence of carcinogenic activity of C.I. Direct Blue 218 in male and female B6C3F1 mice based on increased incidences of hepatocellular adenomas and carcinomas. The occurrence of a few neoplasms of the kidney and small intestine in male mice may have been related to C.I. Direct Blue 218 treatment. The administration of C.I. Direct Blue 218 produced an increased incidence of forestomach basal cell hyperplasia in rats and hepatocellular foci of cytologic alteration in mice. Synonyms: cuprate(4-), [mu-[(3,3'-dihydroxy[1,1'-biphenyl]-4,4'-diyl)bis[5-amino-4-hydroxy- 2,7-naphthalnedisulfonato]](8-)]]di-, tetrasodium; copper, [tetrahydrogen-3,3'-[(3,3'-dihydroxy-4,4'-biphenylylene)bis(azo)]bis [5-amino-4-hdroxy-2,7-naphthalenedisulfonato](4-)]di-, tetrasodium salt; 1-naphthol-3,6-disulfonic acid, 2,2'-(3,3'-dihydroxy-4,4'-biphenylylenebisazo)bis [8-amino-, dicopper deriv., tetrasodium salt
 ...
PMID:NTP Toxicology and Carcinogenesis Studies of C.I. Direct Blue 218 (CAS No. 28407-37-6) in F344/N Rats and B6C3F1 Mice (Feed Studies). 1261 1

Increases in proliferin (PLF) gene family mRNA abundance and promotional effects in cell transformation assays are paired responses that follow exposures to diverse chemical and physical agents in the C3H/10T1/2 in vitro model of multi-stage carcinogenesis. This study measured PLF mRNA abundance changes over 1 to 3 d in response to several types of promoters that were previously unassessed for this effect. Saccharin is a known promoter of cell transformation in C3H/10T1/2 cell cultures, but unlike 12-O-tetradecanoylphorbol 13-acetate (TPA) or mezerein, PLF mRNA abundance increases were inconsistently detected following simple addition of saccharin to the culture medium. Consistent effects occurred when pretreatments with promoting concentrations of saccharin or sodium saccharin (1-13 mM) were combined with subsequent additions of serum or complete medium changes. When added at or near their lowest observed effect levels (LOELs) for transformation, other promoters of 10T1/2 cells such as formaldehyde (50-100 microM), diethylstilbesterol (DES) (0.5-30 microM), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) (4-40 pM) were shown to be inducers of both basal and serum-induced PLF mRNA levels. Acetaldehyde (300-900 microM) was comparable to formaldehyde as an inducer. In contrast to these various promoters, pretreatment with phenobarbital or methanol, both non-promoters in these cells, did not affect serum-induced PLF mRNA levels at concentrations up to 3 mM and 2 M, respectively. The published values for the LOELs of 17 promoters of cell transformation and the LOELs determined to date for PLF mRNA induction were highly correlated over a 1 billion - fold concentration range. The response of PLF mRNA is a short-term marker sensitive to the active concentration ranges of diverse chemical agents with promotional activity in C3H/10T1/2 cell transformation system.
 ...
PMID:Combined effects of tumor promoters and serum on proliferin mRNA induction: a biomarker sensitive to saccharin, 2,3,7,8-TCDD, and other compounds at minimal concentrations promoting C3H/10T1/2 cell transformation. 1451 35

Long-term occupational exposure to formaldehyde (FA) increases the risk for nasopharyngeal squamous cell carcinoma. As the skin is also in contact with FA by environmental exposure, we tested the genotoxic properties of appropriate low concentrations (<100 microM) of FA on cultured keratinocytes and fibroblasts of human skin. The initial DNA damage was assessed by comet assay. The induction of DNA protein crosslinks was measured by the ability of FA to reduce DNA migration induced by methyl-methane-sulfonate. Upon 4 h of exposure to FA, significant (P < 0.05) crosslink formations were observed in fibroblasts (50 microM FA) and in keratinocytes (25 microM FA). Upon 8 h of exposure to FA (25 microM FA), significant crosslink formations were observed in both the cell types. FA is known to inhibit different DNA repair pathways. Therefore, we studied the effect of FA on UV-induced repair. Human keratinocytes and fibroblasts exposed to 10 microM FA prior to UV irradiation showed disturbed repair kinetics after UVC and UVB, but not after UVA irradiation. Single-strand breaks (SSBs) derived from nucleotide excision repair disappeared 6 h after solely UVC (3 mJ/cm2) or 3 h solely UVB (30 mJ/cm2) exposure in both the cell types. In the presence of FA, SSBs were still present at these time points containing a reference to a delay in DNA resynthesis/ligation. FA at a concentration not inducing micronuclei (12.5 microM) caused significant increase of UVC-induced (4 mJ/cm2) chromosomal damage. Proliferation of keratinocytes and fibroblasts was in parallel to observed DNA damages. In conclusion, our data suggest that environmental exposure to FA may contribute to UV-induced skin carcinogenesis.
 ...
PMID:Low concentrations of formaldehyde induce DNA damage and delay DNA repair after UV irradiation in human skin cells. 1514 21

Because of potential exposure both in the workplace and from ambient air, the known carcinogen 1,3-butadiene (BD) is considered a priority hazardous air pollutant. BD and its 2-methyl analog, isoprene (ISO), are chemically similar but have very different toxicities, with ISO showing no significant carcinogenesis. Once released into the atmosphere, reactions with species induced by sunlight and nitrogen oxides convert BD and ISO into several photochemical reaction products. In this study, we determined the relative toxicity and inflammatory gene expression induced by exposure of A549 cells to BD, ISO, and their photochemical degradation products in the presence of nitric oxide. Gas chromatography and mass spectrometry analyses indicate the initial and major photochemical products produced during these experiments for BD are acrolein, acetaldehyde, and formaldehyde, and products for ISO are methacrolein, methyl vinyl ketone, and formaldehyde; both formed < 200 ppb of ozone. After exposure the cells were examined for cytotoxicity and interleukin-8 (IL-8) gene expression, as a marker for inflammation. These results indicate that although BD and ISO alone caused similar cytotoxicity and IL-8 responses compared with the air control, their photochemical products significantly enhanced cytotoxicity and IL-8 gene expression. This suggests that once ISO and BD are released into the environment, reactions occurring in the atmosphere transform these hydrocarbons into products that induce potentially greater adverse health effects than the emitted hydrocarbons by themselves. In addition, the data suggest that based on the carbon concentration or per carbon basis, biogenic ISO transforms into products with proinflammatory potential similar to that of BD products.
 ...
PMID:Effects of 1,3-butadiene, isoprene, and their photochemical degradation products on human lung cells. 1553 32

The adenomatous polyposis coli gene (APC gene) originally was identified as a tumor suppressor gene in colon cancer. We reported previously that APC is mutated and/or deleted in primary oral squamous cell carcinoma (OSCC) tissues and suggested that loss of APC function contributes to carcinogenesis in the oral region. In this study, we examined 50 OSCC tissue samples, which had been fixed in 10% buffered formaldehyde solution and embedded in paraffin, and eight cell lines, which were derived from OSCC, to analyze the expression level of the APC gene. Significant down-regulation of APC was detected by immunohistochemistry in 15 (30.0%) of 50 tissue samples and by the reverse transcriptase-polymerase chain reaction in five (62.5%) of eight cell lines. We then investigated the status of APC gene promoter methylation and restoration of the APC gene mRNA. Hypermethylation of the APC promoter CpG island was detected in two of eight (25%) OSCC-derived cell lines, and APC gene mRNA was restored in all OSCC-derived cell lines showing down-regulation of gene expression (n=5) after treatment with 5-aza-2'-deoxycytidine, a DNA demethylating agent. Thus, the contribution of down-regulated APC expression to the development of human OSCC was about 30%, and hypermethylation of the gene promoter CpG island was confirmed to be a significant mechanism of inactivation of the APC gene in oral carcinogenesis.
 ...
PMID:Status of reduced expression and hypermethylation of the APC tumor suppressor gene in human oral squamous cell carcinoma. 1575 20

Concern has been expressed about the safety of formocresol use in pediatric dentistry. Formaldehyde, a primary component in formocresol, is a hazardous substance and is considered a probable human carcinogen by Health Canada. However, humans inhale and ingest formaldehyde daily and also produce this compound as part of normal cellular metabolism. The human body is physiologically equipped to handle this exposure through multiple pathways for oxidation of formaldehyde to formate and incorporation into biological macromolecules via tetrahydrofolate-dependent one-carbon biosynthetic pathways. Recent re-evaluation of earlier research that examined potential health risks associated with formaldehyde exposure has shown that the research was based on flawed assumptions, which resulted in erroneous conclusions. This review examines more recent research about formaldehyde metabolism, pharmacokinetics and carcinogenicity, the results of which indicate that formaldehyde is probably not a potent human carcinogen under conditions of low exposure. Extrapolation of these research results to pediatric dentistry suggests an inconsequential risk of carcinogenesis associated with formaldehyde use in pediatric pulp therapy. Areas for further investigation are suggested.
 ...
PMID:Persuasive evidence that formocresol use in pediatric dentistry is safe. 1669 91

Urinary bladder transitional epithelium is the main site of bladder cancer, and the use of transitional cells to study carcinogenesis/genotoxicity is recommended over the use of whole bladders. Because the transitional epithelium is only a small fraction of the whole bladder, the alkaline single cell gel electrophoresis assay (Comet assay), which requires only a small number of cells per sample, is especially suitable for measuring DNA damage in transitional cells. However, existed procedures of cell collection did not yield transitional cells with a high purity, and pooling of samples was needed for Comet assay. The goal of this study was to develop an optimized protocol to evaluate DNA damage in the urinary bladder transitional epithelium. This was achieved by an enzymatic stripping method (trypsin-EDTA incubation plus gentle scraping) to selectively harvest transitional cells from rat bladders, and the use of the alkaline Comet assay to detect DNA strand breaks, alkaline labile sites, and DNA-protein crosslinks. Step by step procedures are reported here. Cells collected from a single rat bladder were sufficient for multiple Comet assays. With this new protocol, increases in DNA damage were detected in transitional cells after in vitro exposure to the positive control agents, hydrogen peroxide or formaldehyde. Repair of the induced DNA damage occurred within 4h. This indicated the capacity for DNA repair was maintained in the harvested cells. The new protocol provides a simple and inexpensive method to detect various types of DNA damage and to measure DNA damage repair in urinary bladder transitional cells.
 ...
PMID:Measurement of DNA damage in rat urinary bladder transitional cells: improved selective harvest of transitional cells and detailed Comet assay protocols. 1768 49


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>