UMLS:C0001430 - FACTA Search

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Query: UMLS:C0001430 (adenoma)
21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A series of organosulfur compounds were synthesized with the aim of developing chemopreventive compounds active against hepatotoxicity and chemical carcinogenesis. 2-(Allylthio) pyrazine (2-AP) was effective in inhibiting cytochrome P450 2E1-mediated catalytic activities and protein expression, and in inducing microsomal epoxide hydrolase and major glutathione S-transferases. 2-AP reduced the hepatotoxicity caused by toxicants and elevated cellular GSH content. Development of skin tumors, pulmonary adenoma and aberrant crypt foci in colon by various chemical carcinogens was inhibited by 2-AP pretreatment. Anticarcinogenic effects of 2-AP at the stage of initiation of tumors were also observed in the aflatoxin B1 (AFB1)-induced three-step medium-term hepatocarcinogenesis model. Reduction of AFB1-DNA adduct by 2-AP appeared to result from the decreased formation of AFB1-8,9-epoxide via suppression of cytochrome P450, while induction of GST by 2-AP increases the excretion of glutathione-conjugated AFB1. 2-AP was a radioprotective agent effective against the lethal dose of total body irradiation and reduced radiation-induced injury in association with the elevation of detoxifying gene expression. 2-AP produces reactive oxygen species in vivo, which is not mediated with the thiol-dependent production of oxidants and that NF-kappa B activation is not involved in the induction of the detoxifying enzymes. The mechanism of chemoprotection by 2-AP may involve inhibition of the P450-mediated metabolic activation of chemical carcinogens and enhancement of electrophilic detoxification through induction of phase II detoxification enzymes which would facilitate the clearance of activated metabolites through conjugation reaction.
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PMID:Chemopreventive effects of 2-(allylthio)pyrazine. 1023 Apr 97

4-Aminobiphenyl (4-ABP), a potent carcinogen in rodents (liver cancer) and human (bladder cancer), is found as an environmental contaminant and in tobacco smoke. Hemoglobin adducts and lung DNA adducts of 4-ABP are found in tobacco smokers. In vitro metabolism studies with human and rat liver microsomes have shown that CYP1A2 is primarily responsible for catalyzing N-hydroxylation, the initial step in the metabolic activation of 4-ABP. To determine whether this P450 is a rate limiting pathway for hepatocarcinogenesis, CYP1A2-null mice were analyzed at 16 months of age and were compared with wild-type mice in their response to 4-ABP using the neonatal mouse bioassay and two different doses of the carcinogen. Overall differences in incidences of hepatocellular adenoma, carcinoma and preneoplastic foci were not significant between either genotypes or 4-ABP doses used, whereas small, but significant, differences were found for specific types of foci. These results suggest that while CYP1A2 levels may not be rate limiting for 4-ABP metabolism to produce tumors and foci, it may modulate the induction process of some types of liver foci in either a positive or negative manner. In vitro studies using CYP1A2-null and wild-type mouse liver microsomes revealed that CYP1A2 is not the sole P450 required for 4-ABP N-hydroxylation and that another, yet to be identified, P450 is likely to be involved.
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PMID:CYP1A2 is not the primary enzyme responsible for 4-aminobiphenyl-induced hepatocarcinogenesis in mice. 1046 30

Chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) is an orphan member of the steroid/thyroid hormone receptor superfamily. COUP-TFII has been demonstrated to negatively regulate the transcriptional activity of adrenal 4-binding protein, a steroidogenic cell-specific transcription factor that activates the transcription of various steroidogenic P450 genes. We therefore examined immunolocalization of COUP-TFII in the human adrenal cortex and its disorders, including functioning and nonfunctioning cortical tumors, to study its possible correlation with adrenocortical steroidogenesis. In nonpathological adrenal cortex, COUP-TFII immunoreactivity was marked in the nuclei of adrenocortical cells in definitive and fetal zones from 16 gestational weeks to 2 months after birth. Immunoreactivity for COUP-TFII was marked in the zona glomerulosa and weak in the zonae fasciculata and reticularis from 7 months to 8 yr of age, but thereafter markedly decreased in these zones (P < 0.05, between age 7 months to 8 yr and 24-62 yr of age, respectively). In adrenocortical tumors, COUP-TFII immunoreactivity was marked in the nuclei of tumor cells of aldosteroma (H score, 134 +/- 15.9; P < 0.001 vs. Cushing's adenoma and P < 0.05 vs. nonfunctioning adenoma and carcinoma), modest in nonfunctioning adenoma (82.7 +/- 19.8) and adrenocortical carcinoma (79.6 +/- 56.3), and low in Cushing's adenoma (38.2 +/- 24.5). Results from immunoblotting performed in seven cases of adenomas were consistent with those of immunohistochemistry. In the attached nonneoplastic adrenal cortex of the adenomas, immunoreactivity for COUP-TFII was markedly increased compared to that in nonpathological adrenal cortex in adults and was especially marked in the zona glomerulosa in the attached adrenal of aldosteroma (P < 0.001) and the zona fasciculata in that of Cushing's adenoma (P < 0.05). COUP-TFII immunoreactivity was universally detected in stromal cells of the adrenal glands. These results suggest that COUP-TFII plays an important role in the regulation of steroidogenesis in human adrenal cortex and its disorders.
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PMID:Chicken ovalbumin upstream promoter transcription factor II in the human adrenal cortex and its disorders. 1094 77

A 43-year-old Japanese woman presented hypertension, hypokalemia and typical Cushingoid signs. Autonomous secretion of both aldosterone and cortisol was shown. Abdominal computed tomography demonstrated a single tumor in the right adrenal gland, which established the diagnosis of combined primary aldosteronism and Cushing's syndrome. The resected tumor was a golden yellow-colored adenoma (diameter 4.3 cm) which expressed P450(aldo) and P450(11beta), causing oversecretion of both hormones from this adenoma. After tumor resection, overproduction of both hormones disappeared and she developed adrenal insufficiency, suggesting the strong suppression of normal adrenal function. This case was complicated by Hashimoto's thyroiditis.
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PMID:Combined primary aldosteronism and Cushing's syndrome due to a single adrenocortical adenoma complicated by Hashimoto's thyroiditis. 1248 54

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant of the heterocyclic amines found in cooked meat. Based on in vitro studies with rats and humans, CYP1A2 is believed to be the primary enzyme responsible for N(2)-hydroxylation, the initial step in the metabolic activation of PhIP. To determine whether CYP1A2 is the primary P450 responsible for metabolic activation of PhIP in mice that leads to tumor formation, neonatal Cyp1a2-null and wild-type mice were treated with approximately 11 (low dose) and approximately 22 (high dose) mg/kg PhIP at days 8 and 15, corresponding cumulatively to 600 and 1200 nmol PhIP, and analyzed at 19-21 months of age. Three major induced tumors were found; lymphomas and tumors in lung and liver. The incidence of lymphoma was higher in Cyp1a2-null females than wild-type females treated with low dose (600 nmol) PhIP whereas no significant differences were observed in other treatment groups of mice. Overall differences in incidences of lung adenoma/adenocarcinoma were in general not consistent among sexes, genotypes and PhIP doses used, although reduced incidences of lung tumors were found in Cyp1a2-null males with low dose (600 nmol) and null females with high dose (1200 nmol) PhIP. Higher incidences of hepatocellular adenoma were observed in Cyp1a2-null female and male mice as compared with wild-type mice. In vitro studies using Cyp1a2-null and wild-type mouse liver microsomes revealed that CYP1A2 is the major enzyme required for PhIP N2-hydroxylation in mouse, the initial metabolic activation of PhIP that is thought to lead to tumor formation. These in vivo and in vitro results suggest that although the metabolic activation of PhIP is carried out primarily by CYP1A2, an unknown pathway unrelated to CYP1A2 appears to be responsible for PhIP carcinogenesis in mouse when examined in the neonatal bioassay. In fact, CYP1A2 may even be protective against all transformation, especially in females.
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PMID:Carcinogenesis of the food mutagen PhIP in mice is independent of CYP1A2. 1266 21

Cushing's syndrome due to bilateral cortisol-secreting adenomas rarely occurs. We present a case of Cushing's syndrome due to bilateral adenomas. Both adenomas had distinct cell compositions, and were compared with emphasis on immunohistochemical and enzyme histochemical analysis for cytochrome P450(11beta) and 3beta-hydroxysteroid dehydrogenase (3betaHSD). A 37 year-old female was diagnosed with ACTH-independent Cushing's syndrome based on physical findings and hormonal evaluation. High-resolution CT scan showed bilateral adrenocortical adenomas and atrophied glands. 131I-methylnorcholesterol incorporation into both glands suggested both adenomas were functional. Clinical diagnosis prior to surgery was ACTH-independent Cushing's syndrome due to functioning bilateral adenomas. The left adrenal gland was totally resected, while the right one was partially resected by laparoscopic approach. Both adenomas were black on cut sections, and were comparatively evaluated by immunohistochemical and enzyme histochemical analysis for P450(11beta) and 3betaSD. The left adenoma was 1.6 cm in diameter and had a complex cellular composition and enzyme expression similar to that of primary pigmented nodular adrenocortical disease (PPNAD), while the right adenoma was 1.8 cm in diameter with compact cells typical of a solitary cortisol-producing adenoma. Adjacent bilateral adrenal cortex showed marked atrophy, but contained several micronodules. Serum cortisol levels, both at basal and after a low dodexamethasone, normalized thirteen months after surgery. In conclusion, the present case of Cushing's syndrome with bilateral adrenal adenomas demonstrated for the first time the simultaneous occurrence of two distinct adenomas, an ordinary cortisol-producing adenoma and a PPNAD-like adenoma. Further case reports of multiple adrenal adenomas should be well-analyzed to clarify whether the results from this case represent a new subgroup of ACTH-independent Cushing's syndrome.
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PMID:Cushing's syndrome due to bilateral adrenocortical adenomas with unique histological features. 1280 35

Hyperfunctioning adrenocortical adenomas produce excessive amounts of various corticosteroids due to dysregulated expression of steroidogenic enzymes. Since no genetic mutations in steroidogenic enzyme genes have been identified as yet, the dysregulated expression at the transcription level may be crucial. Chicken ovalbumin upstream promoter-transcription factors (COUP-TFs) and steroidogenic factor-1 (SF-1) play key roles in the transcriptional regulation of steroidogenic P450 genes. Transfection studies showed that SF-1 activated and COUP-TFs repressed the transcription of bovine CYP17 gene promoter from the CRS2 element in a mutually exclusive manner in Y-1 cells. The results indicate that COUP-TFs negatively regulate the transcriptional activity of SF-1, a steroidogenic cell-specific activator of various steroidogenic P450 genes. Expression of both COUP-TFI and COUP-TFII was significantly decreased in the cortisol-producing adenomas, in which CYP17 was drastically overexpressed, indicating that decreased expression of COUP-TFs play a key role in overexpression of CYP17 in this type of tumors. We then screened for COUP-TFI-interacting proteins from a cortisol-producing adenoma cDNA library using a yeast two-hybrid system and identified a novel RING finger-containing protein which can function as a coregulator for COUP-TFI. Notably, COUP-TFI activated rather than repressed several target genes including the human CYP11B2 gene promoter, the results of which were opposite to those of the CYP17 promoter. The bifunctional activities of COUP-TFI may be derived from the promoter context and our newly identified COUP-TFI coregulator.
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PMID:Regulation of differential COUP-TF-coregulator interactions in adrenal cortical steroidogenesis. 1294 35

Urethane is a carcinogen to which there is widespread exposure through the consumption of fermented foods and alcoholic beverages. In this study, we have assessed the carcinogenicity of urethane in combination with ethanol. Male and female B6C3F(1) mice (48 mice per sex per group) were exposed to 0, 10, 30, or 90 ppm urethane in the presence of 0%, 2.5%, or 5% ethanol in drinking water ad libitum for two years, at which time the extent of tumorigenesis was assessed. Additional mice (four per sex per group) received the same doses for four weeks to assess serum levels of urethane and ethanol, DNA adduct formation, and the induction of microsomal cytochromes P450, cell proliferation, and apoptosis. Urethane decreased cell replication in the livers of female, but not male, mice, decreased cell replication in the lungs of both sexes, and induced cytochrome P450 2E1 in the livers of female mice. Hepatic levels of the DNA adduct 1,N(6)-ethenodeoxyadenosine were increased by exposure to urethane and decreased by treatment with ethanol. Animal weights and survival were not affected by ethanol; in contrast, urethane administration decreased body weights and survival. Urethane caused dose-dependent increases in liver, lung, and harderian gland adenoma or carcinoma and hemangiosarcoma of the liver and heart in both sexes, mammary gland and ovarian tumors in females, and squamous cell papilloma or carcinoma of the skin and forestomach in males. The increase in hepatocellular tumors occurred in a relatively linear manner and was attributed to the formation of 1,N(6)-ethenodeoxyadenosine in hepatic DNA coupled with an increase in cell replication. Hemangiosarcomas were observed only at the 90 ppm urethane dose and were probably a result of high-dose urethane-induced toxicity. Lung alveolar/bronchiolar and harderian gland adenoma or carcinoma increased in a relatively linear manner, suggestive of a genotoxic mechanism for tumor induction. Ethanol induced a dose-dependent trend in hepatocellular adenoma or carcinoma in male mice, with the incidence being marginally increased at the highest dose. In female mice administered 10 ppm and 90 ppm urethane, ethanol caused dose-related increases in alveolar/bronchiolar adenoma or carcinoma and hemangiosarcoma of the heart, respectively. This may be due to ethanol decreasing the first-pass clearance of urethane, thus, increasing systemic distribution. In male mice a different relationship was observed: ethanol caused a dose-related decrease in alveolar/bronchiolar and harderian gland adenoma or carcinoma in mice administered 30 ppm urethane.
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PMID:Effect of ethanol on the tumorigenicity of urethane (ethyl carbamate) in B6C3F1 mice. 1558 91

Recently we reported that the occurrence of lung adenoma caused by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was completely prevented by pretreatment of female A/J mice with 8-methoxypsoralen, a potent inhibitor of cytochrome P450 (P450 or CYP) 2A [Takeuchi et al. (2003) Cancer Res., 63, 7581-7583]. Thus, the aim of this study was to confirm that 8-methoxypsoralen exhibits chemopreventive effects by inhibiting CYP2A in the mouse lung. The involvement of CYP2A in the metabolic activation of NNK in the lung was first evidenced by the fact that the mutagenic activation of NNK by mouse lung microsomes was inhibited by 8-methoxypsoralen, coumarin and antibodies to rat CYP2A1. Supporting this, the mutagenic activation of NNK was efficiently catalyzed by mouse CYP2A4 and CYP2A5 co-expressed with NADPH-P450 reductase in a genetically engineered Salmonella typhimurium YG7108. The expression of mRNA for CYP2A5, but not for CYP2A4 or CYP2A12, in the mouse lung was proven by reverse transcriptase-polymerase chain reaction, probably indicating that CYP2A5 present in the mouse lung was involved in the metabolic activation of NNK. In accordance with these in vitro data, treatment of gpt delta transgenic mice with 8-methoxypsoralen prior to NNK completely inhibited the mutation of the gpt delta gene. The in vivo chemopreventive effects of 8-methoxypsoralen towards NNK-induced adenoma was seen only when the agent was given to female A/J mice prior to, but not posterior to, NNK, lending support to the idea that NNK is activated by CYP2A5 in the mouse lung as an initial step to cause adenoma. The inhibition by 8-methoxypsoralen of NNK-induced adenoma was seen in a dose-dependent manner: the dose to show apparent 50% suppression was calculated to be 1.0 mg/kg. To our surprise, CYP2A protein(s) was expressed in the lesion of NNK-induced lung adenomas, probably suggesting that 8-methoxypsoralen could inhibit the possible occurrence of further mutation of the adenoma cells induced by NNK. Based on these lines of evidence, we propose that 8-methoxypsoralen inhibits the CYP2A5-mediated metabolic activation of NNK in the mouse lung, leading to the prevention of NNK-induced adenoma.
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PMID:Mechanisms of chemopreventive effects of 8-methoxypsoralen against 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced mouse lung adenomas. 1595 17

DIOXIN TOXIC EQUIVALENCY FACTOR EVALUATION OVERVIEW: Polyhalogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have the ability to bind to and activate the ligand-activated transcription factor, the aryl hydrocarbon receptor (AhR). Structurally related compounds that bind to the AhR and exhibit biological actions similar to TCDD are commonly referred to as "dioxin-like compounds" (DLCs). Ambient human exposure to DLCs occurs through the ingestion of foods containing residues of DLCs that bioconcentrate through the food chain. Due to their lipophilicity and persistence, once internalized they accumulate in adipose tissue resulting in chronic lifetime human exposure. Since human exposure to DLCs always occurs as a complex mixture, the Toxic Equivalency Factor (TEF) methodology has been developed as a mathematical tool to assess the health risk posed by complex mixtures of these compounds. The TEF methodology is a relative potency scheme that ranks the dioxin-like activity of a compound relative to TCDD that is the most potent congener. This allows for the estimation of the potential dioxin-like activity of a mixture of chemicals, based on a common mechanism of action involving an initial binding of DLCs to the AhR. The toxic equivalency of DLCs was nominated for evaluation, because of the widespread human exposure to DLCs and the lack of data on the adequacy of the TEF methodology for predicting relative potency for cancer risk. To address this, the National Toxicology Program conducted a series of 2-year bioassays in female Harlan Sprague-Dawley rats to evaluate the chronic toxicity and carcinogenicity of DLCs and structurally-related polychlorinated biphenyls (PCBs) and mixtures of these compounds. 3,3',4,4',5-Pentachlorobiphenyl (PCB 126) was produced commercially before 1977 for the electric industry as a dielectric insulating fluid for transformers and capacitors. Manufacture and use of the chemical was stopped because of increased PCB residues in the environment, but it continues to be released into the environment through the use and disposal of products containing PCBs, as by-products during the manufacture of certain organic chemicals, and during combustion of some waste materials. Bioaccumulation of PCB 126 results in persistent levels in animal and human tissues and the biological responses to PCB 126 are similar to those of TCDD, a known human carcinogen. PCB 126 was selected for study by the National Toxicology Program as a part of the dioxin TEF evaluation to assess the cancer risk posed by complex mixtures of polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and PCBs. The dioxin TEF evaluation includes conducting multiple 2-year rat bioassays to evaluate the relative chronic toxicity and carcinogenicity of DLCs, structurally related PCBs, and mixtures of these compounds. PCB 126 was included since this is the most potent coplanar PCB that has dioxin-like activities. While one of the aims of the dioxin TEF evaluation was a comparative analysis across studies, in this Technical Report only the results of the PCB 126 study are presented and discussed. Female Harlan Sprague-Dawley rats were administered PCB 126 (99% pure) in corn oil with acetone by gavage for 14, 31, or 53 weeks or 2 years. 2-YEAR STUDY: Groups of 81 female rats were administered 30, 100, 175, 300, 550, or 1,000 ng PCB 126/kg body weight in corn oil:acetone (99:1) by gavage, 5 days per week, for up to 104 weeks; a group of 81 vehicle control female rats received the corn oil/acetone vehicle alone. A group of 28 rats received 10 ng/kg for up to 53 weeks only. Up to 10 rats per group were evaluated at 14, 31, or 53 weeks. A stop-exposure group of 50 female rats was administered 1,000 ng/kg PCB 126 in corn oil:acetone (99:1) by gavage for 30 weeks then the vehicle for the remainder of the study. Mean body weights of 30 and 100 ng/kg rats were similar to those of the vehicle controls during most of the study, mean body weights of 175 and 300 ng/kg rats were less than those of the vehicle controls during year 2 of the study, and mean body weights of 550 ng/kg, 1,000 ng/kg core study, and 1,000 ng/kg stop-exposure rats were less than those of the vehicle controls after week 17. THYROID HORMONE CONCENTRATIONS: Alterations in serum thyroid hormone levels were evaluated at the 14-, 31- and 53- week interim evaluations. In the 550 and 1,000 ng/kg rats, total thyroxine (T4) and free T4 were significantly lower than vehicle controls and serum triiodothyronine (T3) and thyroid stimulating hormone (TSH) levels were significantly higher than vehicle controls at the 14-week interim evaluation. Serum T3 was also significantly higher in the 300 ng/kg rats compared to vehicle controls at 14 weeks. At 31 weeks, T3 was significantly higher at doses of 100 ng/kg or greater compared to vehicle controls. TSH levels were higher in 550 and 1,000 ng/kg rats than in vehicle controls. At 53 weeks, significantly lower serum concentrations of total T4 and free T4 were observed compared to vehicle controls in groups administered 175 ng/kg or greater and 30 ng/kg or greater, respectively. Serum T3 levels were significantly higher at doses of 175 ng/kg or greater compared to vehicle controls. No changes in TSH were observed between vehicle controls and dosed rats at 53 weeks. HEPATIC CELL PROLIFERATION DATA: To evaluate hepatocyte replication, analysis of labeling of replicating hepatocytes with 5-bromo-2'-deoxyuridine was conducted at the 14-, 31-, and 53-week interim evaluations. The hepatocellular labeling index was significantly higher at doses of 300 ng/kg or greater at 14 weeks and 175 ng/kg or greater at 31 weeks compared to vehicle controls. No statistically significant differences were observed between vehicle controls and PCB 126 dosed rats at 53 weeks. However at 53 weeks, a 5.8-fold increase above the vehicle controls was observed in the 1,000 ng/kg group. CYTOCHROME P450 ENZYME ACTIVITIES: To evaluate the expression of known dioxin-responsive genes, CYP1A1 associated 7-ethoxyresorufin-O-deethylase (EROD) activity and CYP1A2-associated acetanilide 4-hydroxylase (A-4-H) activity were evaluated at the 14-, 31-, and 53-week interim evaluations. In addition, CYP2B associated pentoxyresorufin-O-deethylase (PROD) activity was also analysed. Hepatic PROD (CYP2B1) and hepatic and pulmonary EROD (CYP1A1) activity were significantly greater in all dosed groups than in vehicle controls at weeks 14, 31, and 53. Hepatic A-4-H (CYP1A2) activity was significantly greater in the 30, 100, 175, 300, 550, and 1,000 ng/kg groups compared to vehicle controls at weeks 14, 31, and 53. DETERMINATIONS of PCB 126 CONCENTRATIONS IN TISSUES: The tissue disposition of PCB 126 was analyzed in the liver, lung, fat, and blood of all rats in vehicle controls and all dosed groups at the 14-, 31-, and 53-week interim evaluations and in 10 rats per group including vehicle controls at the end of the 2-year study (104 weeks). Detectable concentrations of PCB 126 were observed in the liver, fat, lung, and blood. Measurable concentrations of PCB 126 were present in the liver and fat at weeks 31, 53, and 104. Hepatic and fat concentrations increased with increasing doses of PCB 126. Measurable concentrations of PCB 126 were present in vehicle control lung tissue at 53 and 104 weeks. No PCB 126 was observed in the blood from the vehicle control rats. Lung and blood concentrations tended to increase with increasing doses of PCB 126, with a few exceptions. In the stop-exposure group, PCB 126 concentrations in liver and fat were lower than the levels observed in the 30 ng/kg group. In the stop-exposure group, lung tissue PCB 126 concentrations were equivalent to the levels observed in the 30 ng/kg group. In blood from the stop-exposure group, PCB 126 concentrations were equivalent to the levels observed in the 100 ng/kg group. PATHOLOGY AND STATISTICAL ANALYSES: Absolute and relative liver weights were significantly increased at all time points and correlated with increased incidences of hepatocellular hypertrophy. At 2 years, there were significant treatment-related increases in the incidences of cholangiocarcinoma and hepatocellular adenoma. Three hepatocholangiomas were seen in the 1,000 ng/kg core study group and a single incidence of cholangioma each occurred in the 550 and 1,000 ng/kg core study groups. At 2 years, a significant dose-related increase in hepatic toxicity was observed and was characterized by increased incidences of numerous lesions including hepatocyte hypertrophy, multinucleated hepatocytes, diffuse fatty change, bile duct hyperplasia, bile duct cyst, oval cell hyperplasia, necrosis, pigmentation, inflammation, nodular hyperplasia, portal fibrosis, cholangiofibrosis, and toxic hepatopathy. The incidences of these lesions were generally decreased in the 1,000 ng/kg stop-exposure group compared to the 1,000 ng/kg core study group. The lung weights of 1,000 ng/kg rats were generally significantly increased at weeks 14, 31, and 53. At 2 years, treatment related increases in the incidences of cystic keratinizing epithelioma and squamous cell carcinomas were observed. In addition, dose-related increases in the incidences of bronchiolar metaplasia of the alveolar epithelium and squamous metaplasia were also observed. The incidence of gingival squamous cell carcinoma of the oral mucosa was significantly increased in the 1,000 ng/kg core study group at 2 years. Gingival squamous cell carcinoma, although reduced in incidence as compared to the 1,000 ng/kg core study group, was still present in the 1,000 ng/kg stop-exposure group. At 2 years, adenomas and/or carcinomas were present in the adrenal cortex of most core study groups and in the 1,000 ng/kg stop-exposure group. Dose-related effects on the incidences of adrenal cortex atrophy and cytoplasmic vacuolization were also seen. (ABSTRACT TRUNCATED)
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PMID:NTP toxicology and carcinogenesis studies of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) (CAS No. 57465-28-8) in female Harlan Sprague-Dawley rats (Gavage Studies). 1662 45

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