8-hydroxy-2--deoxyguanosine and Adenoma

The exact antineoplastic effects of calcium and vitamin D(3) in the human colon are unclear. Animal and in vitro studies show that these two agents reduce oxidative stress; however, these findings have never been investigated in humans. To address this, we conducted a pilot, randomized, double-blind, placebo-controlled, 2 x 2 factorial clinical trial to test the effects of calcium and vitamin D(3) on a marker of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine (8-OH-dG), in the normal colorectal mucosa. Patients (N = 92) with at least one pathology-confirmed colorectal adenoma were treated with 2 g/d calcium and/or 800 IU/d vitamin D(3) versus placebo over 6 months. Overall labeling and colorectal crypt distribution of 8-OH-dG in biopsies of normal-appearing rectal mucosa were detected by standardized automated immunohistochemistry and quantified by image analysis. After 6 months of treatment, 8-OH-dG labeling along the full lengths of colorectal crypts decreased by 22% (P = 0.15) and 25% (P = 0.10) in the calcium and vitamin D(3) groups, respectively, but not in the calcium plus vitamin D(3) group. The estimated treatment effects were strongest among participants with higher baseline colon crypt vitamin D receptor expression (P = 0.05). Overall, these preliminary results indicate that calcium and vitamin D(3) may decrease oxidative DNA damage in the normal human colorectal mucosa, support the hypothesis that 8-OH-dG labeling in colorectal crypts is a treatable oxidative DNA damage biomarker of risk for colorectal neoplasms, and provide support for further investigation of calcium and vitamin D(3) as chemopreventive agents against colorectal neoplasms.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adenoma; Adult; Aged; Biomarkers, Tumor; Calcium Carbonate; Calcium, Dietary; Cholecalciferol; Deoxyguanosine; Dietary Supplements; DNA Damage; Double-Blind Method; Female; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Intestinal Mucosa; Intestinal Neoplasms; Male; Middle Aged; Oxidative Stress; Pilot Projects; Precancerous Conditions

Clinically non-functioning pituitary adenomas (NFPA) are common tumours of the pituitary gland and are mainly considered as benign. The primary aim of this study was to research the effects of NFPA on genome instability in patients with non-functioning pituitary adenoma by using the cytokinesis-block micronucleus cytome (CBMN-cyt) assay and 8-hydroxy- 2'-deoxyguanosine (8-OHdG) assay. The second objective of this study was to assess whether there is a relationship between age, pituitary adenoma diameters, 8-OHDG levels, CBMN site assay parameters, and tumour aggressiveness.. The study was performed on 30 patients who had been diagnosed with NFPA and were admitted to the Department of Endocrinology and Metabolism, and 20 healthy subjects of similar age and sex.. Micronucleus (MN), nucleoplasmic bridges (NPBs), nuclear bud (NBUD) frequencies, and apoptotic and necrotic cell frequencies in patients with NFPA were found to be significantly higher than in control subjects, and plasma 8-OHdG levels in patients with NFPA were statistically significantly lower than control subjects in this study.. It is believed that this is the first study to evaluate the aggressiveness of tumour with chromosome/oxidative DNA damage in patients with NFPA. However, further studies are needed in order to understand the cause of NFPA aggression and to evaluate these patients in terms of risk of cancer.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adenoma; Chromosomes; DNA Damage; Humans; Micronucleus Tests; Oxidative Stress; Pituitary Neoplasms

The carcinogenic potential of phenobarbital (PB) was assessed in a mouse line carrying a mutant

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adenoma; Animals; Apoptosis; Cell Proliferation; Deoxyguanosine; Disease Progression; DNA Glycosylases; Female; Immunohistochemistry; Liver Neoplasms; Male; Mice, Inbred C57BL; Mice, Mutant Strains; Models, Biological; NF-E2-Related Factor 2; Phenobarbital; Survival Analysis; Tandem Mass Spectrometry

Chronic inflammation has been recognized as a contributing factor in the pathogenesis of lung cancer. In this process, reactive oxygen species released by neutrophils may play an important role. The aim of the present study was to investigate the capacity of the major neutrophilic oxidant hypochlorous acid (HOCl), which is formed by myeloperoxidase (MPO), to induce DNA damage and mutagenicity in lung cells. HOCl was mutagenic in lung epithelial A549 cells in vitro, showing at physiological concentrations a significant induction of mutations in the HPRT gene. We studied three major types of DNA lesions that could be relevant for this HOCl-induced mutagenicity. Single strand DNA breakage and 8-oxo-7,8-dihydro-2'-deoxyguanosine were not found to be increased following HOCl treatment. On the other hand, HOCl caused a significant increase in the formation of 3-(2-deoxy-beta-D-erythro-pentofuranosyl)pyrimido[1,2-alpha]purin-10(3H)-one (M(1)dG), which can be formed by either malondialdehyde (MDA) or base propenals. We observed an increased MDA formation upon exposure of A549 cells to HOCl, but a role of base propenals cannot be excluded. In line with this, we observed 4-fold increased M(1)dG adduct levels in mice that were intratracheally instilled with lipopolysaccharide to induce a pulmonary inflammation with neutrophil influx. Depletion of circulating neutrophils significantly reduced pulmonary MPO activity as well as M(1)dG adducts levels, thereby providing a causal link between neutrophils/HOCl and pulmonary genotoxicity in vivo. Taken together, these data indicate that MPO catalysed formation of HOCl during lung inflammation should be considered as a significant source of neutrophil-induced genotoxicity.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adenoma; Animals; Cells, Cultured; Colony-Forming Units Assay; Deoxyguanosine; DNA Adducts; DNA Breaks, Single-Stranded; DNA Damage; Humans; Hypochlorous Acid; Hypoxanthine Phosphoribosyltransferase; Inflammation; Lipid Peroxidation; Lipopolysaccharides; Lung; Lung Neoplasms; Male; Malondialdehyde; Mice; Mice, Inbred C57BL; Mutation; Neutrophils; Oxidants; Peroxidase; Purine Nucleosides

This study assessed the presence of oxidative damage and lipid peroxidation in thyroid neoplasia.. Using tissue microarrays and immunohistochemistry, we assessed levels of DNA damage (8-oxo-dG) and lipid peroxidation (4-HNE) in 71 follicular thyroid adenoma (FTA), 45 papillary thyroid carcinoma (PTC), and 17 follicular thyroid carcinoma (FTC) and matched normal thyroid tissue.. Cytoplasmic 8-oxo-dG and 4-HNE expression was significantly higher in FTA, FTC, and PTC tissue compared to matched normal tissue (all p values < .001). Similarly, elevated nuclear levels of 8-oxo-dG were seen in all in FTA, FTC, and PTC tissue compared to matched normal (p values < .07, < .001, < .001, respectively). In contrast, a higher level of 4-HNE expression was detected in normal thyroid tissue compared with matched tumor tissue (p < .001 for all groups). Comparing all 3 groups, 4-HNE levels were higher than 8-oxo-dG levels (p < .001 for all groups) except that cytoplasmic levels of 8-oxo-dG were higher than 4-HNE in all (p < .001). These results were independent of proliferation status.. High levels of DNA damage and lipid peroxidation in benign and malignant thyroid neoplasia indicates this damage is an early event that may influence disease progression.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adenoma; Adolescent; Adult; Aged; Aldehydes; Antibodies, Monoclonal; Cytoplasm; Deoxyguanosine; DNA Damage; Female; Humans; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Protein Array Analysis; Thyroid Neoplasms; Young Adult

Oxidative stress is involved in the pathogenesis of colon cancer. We wanted to elucidate at which stage of the disease this phenomenon occurs. In the examined groups of patients with colorectal cancer (CRC, n = 89), benign adenoma (AD, n = 77) and healthy volunteers (controls, n = 99), we measured: vitamins A, C and E in blood plasma, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanine (8-oxoGua) in leukocytes and urine, leukocyte 8-oxoGua excision activity, mRNA levels of APE1, OGG1, 8-oxo-7,8-dihydrodeoxyguanosine 5'-triphosphate pyrophosphohydrolase (MTH1) and OGG1 polymorphism. The vitamin levels decreased gradually in AD and CRC patients. 8-OxodG increased in leukocytes and urine of CRC and AD patients. 8-OxoGua was higher only in the urine of CRC patients. 8-OxoGua excision was higher in CRC patients than in controls, in spite of higher frequency of the OGG1 Cys326Cys genotype, encoding a glycosylase with decreased activity. mRNA levels of OGG1 and APE1 increased in CRC and AD patients, which could explain increased 8-oxoGua excision rate in CRC patients. MTH1 mRNA was also higher in CRC patients. The results suggest that oxidative stress occurs in CRC and AD individuals. This is accompanied by increased transcription of DNA repair genes, and increased 8-oxoGua excision rate in CRC patients, which is, however, insufficient to counteract the increased DNA damage.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adenoma; Adenomatous Polyps; Adult; Aged; Aging; Antioxidants; Carcinoma; Case-Control Studies; Colonic Neoplasms; Deoxyguanosine; DNA Glycosylases; DNA Repair; DNA Repair Enzymes; DNA-(Apurinic or Apyrimidinic Site) Lyase; DNA, Neoplasm; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Middle Aged; Neoplasm Staging; Oxidative Stress; Phosphoric Monoester Hydrolases; Polymorphism, Single Nucleotide; RNA, Messenger; Sex Characteristics; Smoking

It has been known for a long time that DNA hypomethylation occurs in many human cancers and precancerous conditions. However, the mechanisms of hypomethylation are largely unknown. It is possible that endogenous 8-oxo-7,8-dihydroguanine (8-oxoGua) level may be linked to aberrant DNA methylation of adjacent cytosine and in this way influences carcinogenesis. Therefore, the aim of the present study was to assess a possible link between 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) background level and 5-methylcytosine content in DNA from human leukocytes of healthy subjects (n=105) as well as in patients with colon adenomas (n=39) and carcinomas (n=50). Our results demonstrated statistically significant negative correlation between background level of 8-oxodG and 5-methylcytosine content in DNA isolated from leukocytes of healthy donors (r=-0.3436, p=0.0003). The mean content of 5-methylcytosine was significantly lower, while 8-oxodG level was significantly higher in leukocytes DNA of patients with colon adenomas and carcinomas in comparison with healthy subjects. The mean values for 5-methylcytosine were: 3.59+/-0.173% (healthy subjects), 3.38+/-0.128% (patients with adenomas), 3.40+/-0.208% (colon cancer patients). The mean values of 8-oxodG in DNA were, respectively: 4.67+/-1.276, 5.72+/-1.787, 5.76+/-1.884 8-oxodG per 10(6) dG molecules. DNA from affected tissue (colon) suffered from significant, about 10% reduction in cytosine methylation in comparison with leukocytes of the paired subjects. Our work provides the first in vivo evidence suggesting that increased levels of 8-oxodG in DNA may lead to carcinogenesis not only via mispair/mutagenic potential of the modified base but also through its ability to influence gene expression by affecting DNA methylation.

Topics: 5-Methylcytosine; 8-Hydroxy-2'-Deoxyguanosine; Adenoma; Adult; Aged; Aged, 80 and over; Carcinoma; Colonic Neoplasms; Cytosine; Deoxyguanosine; DNA Damage; Female; Humans; Leukocytes; Male; Middle Aged

To clarify the in vivo genotoxic potential of kojic acid (KA), formation of DNA adducts and 8-hydroxy-deoxyguanosine (8-OHdG) in the thyroids of male rats subjected to dietary administration of 2% KA for 2 weeks were assessed by 32P-postlabeling analysis and with a high-performance liquid chromatography system coupled to an electrochemical detector (ECD), respectively. In addition, to investigate possible tumor initiation activity, male F344 rats were given diet containing 0, 0.02, 0.2 or 2% kojic acid for 8 weeks followed by administration of 0.1% sulfadimethoxine (SDM), a thyroid tumor promoter, in the drinking water for 23 weeks with a subsequent 13-week recovery period (two-stage thyroid tumorigenesis model). Rats given four times by s.c. injection of N-bis(2-hydroxypropyl)nitrosamine (DHPN; 700 mg/kg bw) during the initiation period followed by administration of 0.1% SDM and rats given diet containing 2% KA for the initial 8 weeks or for the entire 31 weeks of the experiment, or basal diet alone were provided as controls. DNA adducts were not formed, and the 8-OHdG level was not increased in the thyroids of rats given 2% KA for 2 weeks. In the two-stage thyroid tumorigenesis model, neither adenomas nor carcinomas were induced in the groups given 0, 0.02, 0.2 or 2% KA followed by 0.1% SDM administration, and incidences and multiplicities of focal follicular cell hyperplasias did not demonstrate any significant intergroup differences at the end of administration and recovery periods. In contrast, incidences and multiplicities of focal follicular cell hyperplasias, adenomas and carcinomas were all significantly increased in the DHPN + 0.1% SDM group. Although the incidences and multiplicities of focal follicular cell hyperplasias in the group given 2% KA for 31 weeks were greater than those in the 2% KA + 0.1% SDM group and an adenoma was observed in a rat at the end of the recovery period, no development of carcinomas was evident at either time point. No thyroid proliferative lesions were induced in the group given 2% KA for the initial 8 weeks only. The results of the present studies indicate that KA has neither in vivo genotoxic potential nor tumor initiation activity in the thyroid, and strongly suggest that the earlier observed thyroid tumorigenic activity of KA is attributable to a non-genotoxic mechanism.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adenoma; Animals; Carcinogens; Carcinoma; Deoxyguanosine; DNA Adducts; Hyperplasia; Male; Pyrones; Rats; Rats, Inbred F344; Thyroid Gland; Thyroid Neoplasms

We investigated the relationship between lung- and skin-tumor promotion and oxidative stress caused by administration of dimethylarsinic acid (DMA(V)) in mice. The incidence of lung tumors induced by lung tumor initiator (4NQO) and DMA(V) were, as well as 8-oxo-2'-deoxyguanosine (8-oxodG), suppressed by cotreatment with (-)epigallocatechin gallate (EGCG). When mice were topically treated with trivalent dimethylated arsenic (DMA(III)), a further reductive metabolite of DMA(V), not only an increase in skin tumors but also an elevation of 8-oxodG in epidermis were observed. These results suggest that tumor promotion due to DMA(V) administration is mediated by DMA(III) through the induction of oxidative stress.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adenoma; Administration, Topical; Animals; Cacodylic Acid; Carcinogenicity Tests; Carcinogens; Deoxyguanosine; Female; Herbicides; Lung Neoplasms; Male; Mice; Mice, Hairless; Oxidative Stress; Skin Neoplasms

Development of hepatocellular carcinomas in rats caused by a choline-deficient, L-amino acid-defined (CDAA) diet, usually associated with fatty liver, fibrosis, cirrhosis and oxidative DNA damage, has been recognized as a useful model of hepatocarcinogenesis caused by endogenous factors. In the present study, in order to further explore involved factors and genes, we established an equivalent model in spontaneous liver tumor-resistant C57BL/6J mice. Six-week-old males and females were continuously fed the CDAA diet and histological liver lesions and oxidative DNA damage due to 8-hydroxydeoxyguanosine (8-OHdG) were examined after 22, 65 and 84 weeks. In male mice, fatty change and fibrosis were evident at 22 weeks, and preneoplastic foci of altered hepatocytes were seen at an incidence of 8/8 (100%) and a multiplicity of 6.6 +/- 4.0 per mouse at 65 weeks. Hepatocellular adenomas and carcinomas developed at incidences of 16/24 (66.7%) and 5/24 (20.8%), and multiplicities of 1.42 +/- 1.32 and 0.29 +/- 0.62, respectively, at 84 weeks. The female mice exhibited resistance to development of these lesions. The CDAA diet also increased 8-OHdG levels in male but not female mice. These results indicate that a CDAA diet causes hepatocellular preneoplastic foci, adenomas and carcinomas associated with fibrosis and oxidative DNA damage in mice, as in rats, providing a hepatocarcinogenesis model caused by endogenous factors in mice.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adenoma; Amino Acids; Animals; Carcinoma; Choline Deficiency; Deoxyguanosine; Female; Liver Cirrhosis, Experimental; Liver Neoplasms; Male; Mice; Mice, Inbred C57BL

The purpose of this study is to examine the carotenoid effects on lung tumorigenesis induced by intratracheal instillation of diesel exhaust particles (DEP) into mice weekly for 20 wk. It was suggested that active oxygen radicals might play an important role in DEP-induced lung tumorigenesis. Mice were divided to 4 groups of diet containing 0.02% of palm oil carotene, 0.02% of beta-carotene, or no carotenoid with or without DEP. The BF group (4% fat) and the HF group (16% fat) were prepared for each diet group. The experimental period was 12 mo. By the administration of palm oil carotene, neither adenocarcinoma nor adenoma was found in the BF group. In the HF group with palm oil carotene, no adenocarcinoma was observed, and adenoma was reduced. Adenoma in the HF group was not greatly reduced by beta-carotene, but rather increased in the BF group. No adenocarcinoma was found in either the BF or the HF groups with beta-carotene. The 8-hydroxydeoxyguanosine/deoxyguanosine ratio in palm carotene groups was lower than in the other groups, while that in beta-carotene groups was not. From these results, palm oil carotene was suggested to prevent lung tumorigenesis by its protective effect on DNA from active oxygen. Beta-carotene was supposed to have different effects from palm oil carotene on lung tumorigenesis. Besides the chemopreventive effect, the growth of mice was inhibited by the administration of palm oil carotene. Further studies are necessary to elucidate the mechanisms of carotenoid effects.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adenocarcinoma; Adenoma; Animals; Antioxidants; beta Carotene; Carotenoids; Deoxyguanosine; Dietary Fats; DNA Damage; Growth; Lung; Lung Neoplasms; Male; Mice; Mice, Inbred ICR; Reactive Oxygen Species; Time Factors; Vehicle Emissions; Vitamins

This study was done to discover the underlying mechanism of the inhibitory effect of sericin against colon tumorigenesis. Mice were fed a diet with 30 g/kg sericin for 115 d, and given a weekly injection of 1,2-dimethylhydrazine (10 mg/kg body weight) for the initial 10 wk. Dietary supplemental sericin caused a 62% reduction in the incidence of colonic adenoma (P<0.05), but did not affect the incidence of colonic adenocarcinoma. Sericin intake significantly reduced the number of colon adenomas. Consumption of sericin significantly reduced the BrdU labeling index of colonic proliferating cells and the expression of colonic c-myc and c-fos. The levels of colonic 8-hydroxydeoxyguanosine, 4-hydroxynonenal, and inducible nitric oxide synthase protein were significantly suppressed by sericin. The results suggest that dietary sericin suppresses the development of colon tumors by reducing oxidative stress, cell proliferation, and nitric oxide production.

Topics: 1,2-Dimethylhydrazine; 8-Hydroxy-2'-Deoxyguanosine; Adenocarcinoma; Adenoma; Aldehydes; Animals; Apoptosis; Carcinogens; Cell Division; Colonic Neoplasms; Deoxyguanosine; Immunohistochemistry; Intestinal Mucosa; Male; Mice; Mice, Inbred ICR; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Oxidative Stress; Peptides, Cyclic; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-myc; Sericins

This study examined the effects of lyophilized black raspberries (BRB) on azoxymethane (AOM)-induced aberrant crypt foci (ACF), colon tumors, and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in male Fischer 344 rats. AOM was injected (15 mg/kg body wt i.p.) once per week for 2 wk. At 24 h after the final injection, AOM-treated rats began consuming diets containing 0%, 2.5%, 5%, or 10% (wt/wt) BRB. Vehicle controls received 5% BRB or diet only. Rats were sacrificed after 9 and 33 wk of BRB feeding for ACF enumeration and tumor analysis. ACF multiplicity decreased 36%, 24%, and 21% (P < 0.01 for all groups) in the 2.5%, 5%, and 10% BRB groups, respectively, relative to the AOM-only group. Total tumor multiplicity declined 42%, 45%, and 71% (P < 0.05 for all groups). Although not significant, a decrease in tumor burden (28%, 42%, and 75%) was observed in all BRB groups. Adenocarcinoma multiplicity decreased 28%, 35%, and 80% (P < 0.01) in the same treatment groups. Urinary 8-OHdG levels were reduced by 73%, 81%, and 83% (P < 0.01 for all groups). These results indicate that BRB inhibit several measures of AOM-induced colon carcinogenesis and modulate an important marker of oxidative stress in the Fischer 344 rat.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adenocarcinoma; Adenoma; Animals; Anthocyanins; Anticarcinogenic Agents; Azoxymethane; Calcium; Cholesterol; Colonic Neoplasms; Coumaric Acids; Deoxyguanosine; Diet; Ellagic Acid; Freeze Drying; Fruit; Oxidative Stress; Rats; Rats, Inbred F344; Rosaceae; Sitosterols

It has been reported that flumequine (FLU) induces hepatic tumors in mice when given orally for 18 months. We investigated possible underlying mechanisms using a two-stage mouse hepatocarcinogenesis model. After initiation with a single intraperitoneal injection of 100 mg/kg body weight diethylnitrosamine (DEN) or saline, male CD-1 mice were given 4000 ppm FLU in the diet or 500 ppm phenobarbital (PB) in drinking water for 9, 19, 24 or 30 weeks. Toxicity, evidenced by centrilobular swollen and polar hepatocytes with fatty droplets, infiltration of inflammatory cells and increased numbers of mitosis in hepatocytes, was apparent in the livers of mice treated with FLU at all time points, but its severity declined towards the termination. FLU did not induce cytochrome P-450 enzymes such as 1A1, 2B1 and 3A2 as assessed immunohistochemically, while positive expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG) was increased in hepatocytes of both DEN + FLU and FLU groups compared with the relevant controls. In animals given PB, eosinophilic swelling of hepatocytes was prominent, and the hepatocytes showed strongly positive reactions for CYP 1A1 and 3A2. Altered cell foci were induced in the livers of FLU-treated animals both with and without DEN initiation, especially the former, and their development paralleled the degree of hepatic toxicity. These results suggest that FLU hepatocarcinogenicity in mice is dependent on hepatotoxic damage and consequently increased cell proliferation. Oxidative damage to DNA may also be a crucial factor.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adenoma; Animals; Anti-Infective Agents; Carcinogenicity Tests; Cell Division; Cytochrome P-450 CYP1A1; Cytochrome P-450 CYP2B1; Cytochrome P-450 Enzyme System; Deoxyguanosine; Diethylnitrosamine; Fluoroquinolones; Immunohistochemistry; Liver; Liver Neoplasms; Male; Mice; Phenobarbital; Proliferating Cell Nuclear Antigen; Quinolizines; Steroid Hydroxylases

Few studies have been conducted focusing on a potential role of reactive oxygen species in tumor cell metabolism. Here we studied human colorectal adenocarcinomas and adenomas to determine whether oxidative stress is imposed on cancer cells in vivo and used specific antibodies against 8-hydroxy-2'-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (HNE)-modified proteins, and 3-nitro-L-tyrosine (3-NT) to determine whether there is an association between oxidative stress and cellular proliferation. Higher levels of oxidative modifications in DNA and proteins were observed in carcinoma cells, but not in adenoma cells, than in the corresponding nontumorous epithelial cells by immunohistochemistry as well as high-performance liquid chromatography (HPLC)-based 8-OHdG determination. The fraction of proliferating cell nuclear antigen-positive cells was proportionally associated in adenocarcinomas with the staining intensities of 8-OHdG and 3-NT. Furthermore, Western blot analysis of the proteins extracted from carcinoma cells revealed several specific proteins modified by HNE or peroxynitrite. Thus we concluded that colorectal carcinoma, but not adenoma cells, are exposed to more oxidative stress than their corresponding nontumorous epithelial cells, regardless of clinical stage and histology, and further that the oxidative stress in carcinoma cells might stimulate cellular proliferation.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adenocarcinoma; Adenoma; Adult; Aged; Aldehydes; Case-Control Studies; Chromatography, High Pressure Liquid; Colorectal Neoplasms; Deoxyguanosine; Epithelial Cells; Female; Humans; Immunohistochemistry; Male; Middle Aged; Nitrates; Oxidants; Oxidative Stress; Reactive Oxygen Species; Time Factors