Non-cancerous Ones Research Articles

Involvement of alveolar macrophages in the formation of 8-oxodeoxyguanosine associated with exogenous particles in human lungs

Lung specimens were collected from 161 non-smoking male patients with carcinoma to determine the deposition of carbon particles and oxidative damage in lung tissues. Morphologically, carbon particles deposited in human lungs with carcinoma were similar to those of diesel exhaust like particles, and mass of particles showed a significant increase with the increasing age of the patients. An increasing age of patient with carcinomas was also associated with 8-oxodeoxy-guanosine (8-oxo-dG) formation, which was analyzed using the HPLC-electrochemical detector method. In addition, it was found that 8-oxo-dG increased in cancerous tissues rather than in non-cancerous ones. To determine whether particles in lung tissues were associated with 8-oxo-dG formation, carbon particles deposited in lung tissues were partially purified by cycling of alkali fusion with 1M KOH; mutagenic chemicals in particles were extracted and excluded by removal with an equal volume of benzene/methanol and dichloromethane. It was also found that 8-oxo-dG was formed by non-mutagenic particles, and enhanced in the in vivo test using mouse rather than in the in vitro using RAW 254.7 tissue cultured cells. The 8-oxo-dG formation in vivo was due to the fact that hydroxyl radicals might be involved with phagocytosis of non-mutagenic particles in inflammatory cells, and the mutation was induced by hydroxylation of guanine residue on DNA. These results were also demonstrated by the occurrence of alveolar macrophages and neutrophils after intratracheal instillation of particles. These observations suggest that small particles from lung cancer patients further promote oxidative damage when used to treat the mouse lung. Especially, particles from which organic chemicals were removed were highly reactive to oxidative damage and formed 8-oxo-dG.

Frequent CYP1A1 expression in gastric cancers and their related lesions

CYP1A1 expression in various tissues of 43 gastric cancer cases was analyzed with frozen tissue array-based immunohistochemical staining (IHC), RT-PCR, Western blot analysis and EROD (7-ethoxyresourfin-O-deethylase) assay. CYP1A1 was detected immunohistochemically in 86% (37/43) of gastric cancers, in both 57% (4/7) of atrophic gastritis and intestinal metaplasia and in 7.7% (1/13) of non-cancerous mucosa. RT-PCR and Western blot analysis revealed coincident results with that of IHC and ruled out possible concurrent CYP1A2 expression. EROD assay showed increased CYP1A1/1B1 activity in either cancer or premalignant tissues but not in non-cancerous ones. The frequencies of CYP1A1 expression are significantly different between non-cancerous and premalignant (P<0.025) or cancer groups (P<0.005), suggesting that CYP1A1 is expressed at relatively early stage of gastrocarcinogenesis and exerts its effects throughout the stepwise oncogenic processes.

Decreased expression of Bid in human hepatocellular carcinoma is related to hepatitis B virus X protein

As a mitochondrial membrane death ligand, Bid oligomerises Bak to release cytochrome C and its deficiency renders hepatocytes resistant to apoptosis induced by Fas. The Bid level in hepatocellular carcinoma (HCC) is unknown. In this report, we examined the expression of Bid protein and mRNA in HCC cancerous tissues and their corresponding non-cancerous ones. The effect of the hepatitis B x protein (HBx) on the expression of Bid was also evaluated by transfecting hepatoma cells with the HBx gene. The results showed that the expression of Bid was significantly lower in cancerous tissues than that in their corresponding non-cancerous tissues. Immunohistochemical study revealed that Bid molecule was mainly localised in hepato-cytoplasm. Some nuclei were also positive for Bid antigen though to a lesser degree. In vitro experiments demonstrated that the expression of Bid in cells transfected with HBx was significantly lower than that in the cells without HBx transfection. This finding suggests that HBx may play a causative role in the reduction of Bid expression in HCC. This in vitro result is, to some degree, supported by clinical data that all the HCC examined are positive for hepatitis B virus (HBV). We conclude from this data that the expression of Bid in HCC is significantly decreased and the reduction of Bid may result from a mechanism associated with HBx, a major hepatocarcinogenic product from HBV. The imbalance of increased anti-apoptosis and decreased pro-apoptosis seen in HCC is a critical mechanism leading to the uncontrolled growth of tumour cells. Therefore, this study suggests that a deficiency in the expression of Bid may contribute to the development of such an imbalance in HCC.

Activities of DNA Turnover and Free Radical Metabolizing Enzymes in Cancerous Human Prostate Tissue

Activities of adenosine deaminase (ADA), 5'nucleotidase (5'NT), xanthine oxidase (XO), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) and levels of thiobarbituric acid reagent substances (TBARS) were measured in 10 cancerous and 10 noncancerous human prostate tissues. Decreased activities of DNA turnover enzymes (ADA and 5'NT), increased activities of GSH-Px and CAT, and unchanged activities of SOD and XO were observed in cancerous prostate tissues compared with those of noncancerous ones. TBARS levels were found to be higher in cancerous tissues than noncancerous ones. In correlation analysis, mostly positive correlations were established between enzyme activities of the cancerous tissues, whereas no meaningful correlations were found between enzyme activities of the noncancerous tissues except for a positive correlation between XO and SOD. The results indicate that the activities of DNA turnover enzymes were reduced, which was possibly an attempt to lower the rate of purine catabolism, and the activities of GSH-Px and CAT enzymes were increased, probably in response to increased free radical stress occurring in cancerous prostate tissues. Increased concentrations of TBARS suggested oxidant stress and thus accelerated peroxidative reactions in the cancerous tissues, even though antioxidant defense mechanisms were activated. These findings suggest that enzymatic antioxidant systems of cancerous prostate tissues cannot sufficiently eliminate oxidant factors and prevent cellular peroxida-tive reactions occurring during the carcinogenic process.

Activities of superoxide dismutase and glutathione peroxidase enzymes in cancerous and non-cancerous human kidney tissues.

The activities of superoxide dismutases (total, cytoplasmic and mitochondrial) and glutathione peroxidase were measured in 10 cancerous and 10 non-cancerous adjacent human kidney tissues. Total (T-SOD) and cytoplasmic (Cu, Zn-SOD) superoxide dismutase and glutathione peroxidase (GSH-Px) activities were found lower in cancerous tissues compared with those of non-cancerous ones. However, no difference was found between the mitochondrial (Mn-SOD) superoxide dismutase activities of the tissues. Similarly, no differences were observed between the enzyme activity values of the tissues at stage I-II and III-IV renal cancer. In correlation analysis the positive relation found between Cu, Zn-SOD and GSH-Px enzymes in the non-cancerous tissues was found to be absent in the cancerous ones. The results suggest that enzymatic free radical defense mechanism is significantly reduced in the cancerous human kidney tissues due to depressed Cu, Zn-SOD and GSH-Px activities.

Activity of the Enzymes Participating in Purine Metabolism of Cancerous and Noncancerous Human Kidney Tissues

In this study, activity of some of the key enzymes participating in purine metabolism was measured in cancerous and noncancerous human kidney tissues from 18 patients with renal cell carcinoma. Twelve cancerous tissues were at stage T1-T2 and 6 tissues were at stage T3-T4. Adenosine deaminase (ADA) and guanase (GUA) activity was increased and xanthine oxidase (XO) activity decreased in cancerous tissues compared to noncancerous ones. No difference was, however, found between 5′-Nucleotidase (5′-NT) activity of the tissues. There were also no statistically meaningful differences between the enzyme activities of the cancerous tissues at stage T1-2 and T3-4. Results suggest that the changes observed in the activity of the enzymes participating in purine metabolism result from accelerated DNA turnover in the cancerous tissues and cells, and these changes might provide selective advantage, possibly by causing acceleration of salvage pathway activity, to the cancer cells to grow and develop more rapidly.

Activities of adenosine deaminase, 5'-nucleotidase, guanase, and cytidine deaminase enzymes in cancerous and non-cancerous human breast tissues.

We measured activities of some DNA turnover enzymes in 9 breast tissues with stage II cancer, 6 breast tissues with stage IIIa cancer, and 9 non-cancerous adjacent breast tissues from the same patients with stage II cancer. We found higher Adenosine Deaminase (ADA) and 5'-Nucleotidase (5'NT) and lower Guanase (GUA) activities in the cancerous tissues compared with the non-cancerous ones. No meaningful differences were however found between Cytidine Deaminase (CD) activities. Regarding the correlation analysis, positive correlations were established between ADA and 5'NT activities of the cancerous tissues (r = 0.45 for the tissues with stage II and r = 0.60 for the tissues with stage IIIa cancer). No meaningful correlations were however found between other enzyme activities. Relating to activity ratios, no meaningful differences were found between ADA/5'NT values in the tissues. GUA/CD ratios were however lower and the other ratios higher in the cancerous tissues. Results indicated that ADA and 5'NT activities increased and GUA activity decreased in the cancerous breast tissues but CD activities did not change in the tissues affected. It has been suggested that increased ADA and 5'NT together with decreased GUA activities might be a physiologic attempt of the cancer cells to provide more substrates needed by cancer cells to accelerate the salvage pathway activity. Furthermore, high ADA activity might also play part in the detoxication process of high amounts of toxic adenosine and deoxyadenosine substrates produced from accelerated purine metabolism in the cancerous tissues.

Impaired enzymatic antioxidant defense mechanism in cancerous human thyroid tissues.

The activities of total superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) enzymes were measured in cancerous and non-cancerous adjacent tissues from 15 patients with follicular thyroid cancer containing single nodule. SOD and GSH-Px activities were found lower but malondialdehyde levels higher in cancerous tissues compared with those of noncancerous ones. However, no difference was found between CAT activities of the tissues. Activity decrease of GSH-Px enzyme in cancerous tissue was greater than that of SOD enzyme. Results suggested that enzymatic free radical defense system was significantly impaired and lipid peroxidation increased in the cancerous human thyroid tissues.

Adenosine deaminase, 5′ nucleotidase, xanthine oxidase, superoxide dismutase, and catalase activities in cancerous and noncancerous human laryngeal tissues

We determined activities of adenosine deaminase (ADA), 5′ nucleotidase (5NT), xanthine oxidase (XO), superoxide dismutase (CuZn SOD), and catalase (CAT) enzymes in 15 human laryngeal tissues with-differentiated squamous cell carcinomas, in 15 corresponding tumor-free adjacent tissues and in 7 normal laryngeal tissues. We found lower ADA and 5NT and higher XO, CuZn SOD, and CAT activities in cancerous tissues than those in corresponding noncancerous ones. In the correlation analysis, we established one positive intercorrelation, which was between ADA activities of tumor tissues and noncancerous adjacent tissues. We also found some significant intracorrelations between enzyme activities of the tissues, all of which were positive in cancerous ones.

Relation of pancreatic duct hyperplasia to carcinoma

In order to find a relationship between ductal hyperplasia and carcinoma of the pancreas, histological and histochemical examinations were made on pancreatic specimens of 1,174 autopsy patients with special attention to the age incidence of the former. Ductal hyperplasia was divided into 3 types; nonpapillary, papillary, and atypical hyperplasia. All three types of hyperplasia and ductal carcinoma showed a similar tinctorial property in mucous histochemistry. In general, atypical hyperplasia was seen in the pancreas having papillary hyperplasia which was found in the pancreas associated with nonpapillary hyperplasia. All three types of hyperplasia were apparently more frequent in cancerous pancreases than in non-cancerous ones. They were also more common in the head of the pancreas than in the body and tail. Age incidence also suggests a sequential change from nonpapillary hyperplasia through papillary and atypical ones to carcinoma.

The Cancer Problem: A Statistical Study

IT is well known that the incidence of cancerous diseases varies considerably in different districts and in different occupations. In this book Mr. Green has attempted to find some factor which will explain this difference in incidence, and he has critically examined the local distribution of cancer in different districts, particularly in Scotland, and the conditions which obtain in those districts. He finds that cancerous districts, as a rule, are particularly associated with the burning of coal as fuel, while in the non-cancerous ones wood or peat is the staple fuel. Thus in Nairn-shire, which has the highest mortality figure from cancer in Scotland, the cancer deaths for the last ten years are confined to a definite area, while the rest of the county (100 square miles) is entirely free, and in the cancerous area coal is entirely or partially used as fuel, while in the non-cancerous area peat is universally used. The same holds good for other parts of the country. Thus, in the Orkneys, which, as a whole, have a cancer mortality slightly above that for Scotland, Stenness has a cancer death-rate of 1 out of 42 from all causes and peat is the only fuel, while in Sanday, where coal alone is burned, the cancer death-rate is 1 out of 9 from all causes. A strange anomaly, however, was met with. In Birsay and in St. Andrews, in the Orkneys, the cancer mortality is practically as great as in Sanday, yet peat only is burned. Investigation showed that the peat used in these two districts is peculiar, being hard and stony and having a high content of sulphur like coal. From these and other facts the author concludes that a high sulphur content of the fuel is the factor correlating it with cancer. It must be admitted that the array of facts and figures produced by Mr. Green entirely favours his main proposition, and it is difficult to arrive at any other conclusion. The Cancer Problem: A Statistical Study. New edition. By C. E. Green. Pp. ix + 140. (Edinburgh and London: W. Green and Son, Ltd., 1917.)