Wojciech Wasowicz

Selenium and cancer: biomarkers of selenium status and molecular action of selenium supplements

BackgroundThe relationship between selenium and cancer involves many different aspects. These include the forms of selenium present in the diet and in the body, their functions and mechanisms of action, and methods employed in assessing an individual’s selenium nutritional status—both in general, and in epidemiological studies of the risk of cancer in relation to diet, as well as in connection with long-term trials for investigating the disease-preventive potential of selenium supplementation.Aim of the reviewTo review different aspects on selenium metabolism, the occurrence of different selenoproteins and their use as biomarkers of selenium status, the results of intervention trials of the cancer-preventive effects of selenium supplementation, the mechanisms of action involved, together with epidemiological findings on relations between the selenium status in the body and risk of cancer.Results and conclusionsThe rapid advance in the knowledge of different selenoproteins and their biological functions has opened up new possibilities for the understanding of the biological effects of selenium supplementation. A wide variety of effects of different forms and doses of selenium has been observed in a number of experimental systems, and it is at present difficult to pinpoint the mechanism that may explain the positive preventive effects of selenium supplementation observed in some human long-term trials. Moreover, additional such trials are needed to define the benefits and risks of different types and doses of selenium supplements which in the future may be implemented for public health reasons. Another necessary focus for future research is a better understanding of the mechanisms by which selenium interferes with the carcinogenesis process.

Selenium status of low-selenium area residents: Polish experience

The concentration of selenium (Se) in human organism varies widely between geographical areas depending on its content in soil and plants, dietary Se intake, bioavailability and retention, mineral interactions and other factors. The study includes healthy inhabitants of different regions of Poland; pregnant women, lactating women, children from 0 to 15 years of age and adults. Systematic determinations allow us to observe changes of the concentration of Se in time, which may be significant for developing preventive action. The results obtained confirm our thesis that Se concentration in the blood of the inhabitants of Poland depends on the region of the country. In recent years, in a considerable number of Polish inhabitants, the concentration of Se in blood plasma has been relatively low-about 50-55 microg/l, and the calculated daily dietary intake about 30-40 microg/day. The low levels of the element in the blood and urine are probably due to its deficiency in the diet.

Genetic polymorphism of xenobiotic metabolising enzymes, diet and cancer susceptibility.

There is increasing evidence identifying the crucial role of numerous dietary components in modifying the process of carcinogenesis. The varied effects exerted by nutrient and non-nutrient dietary compounds on human health and cancer risk are one of the new challenges for nutritional sciences. In the present paper, an attempt is made to review the most recent epidemiological data on interactions between dietary factors and metabolic gene variants in terms of cancer risk. The majority of case-control studies indicate the significant relationship between cancer risk and polymorphic xenobiotic metabolising enzymes in relation to dietary components. The risk of colorectal cancer is associated not only with CYP2E1 high-activity alleles, but also GSTA1 low-activity alleles, among consumers of red or processed meat. Genetic polymorphisms of NAT1 and NAT2 may be also a breast-cancer susceptibility factor among postmenopausal women with a high intake of well-done meat. On the other hand, phytochemicals, especially isothiocyanates, have a protective effect against colorectal and lung cancers in individuals lacking GST genes. Moreover, polymorphism of GSTM1 seems to be involved in the dietary regulation of DNA damage. The European Prospective Investigation into Cancer and Nutrition study shows a significant inverse association between the polycyclic aromatic hydrocarbon-DNA adduct level and dietary antioxidants only among GSTM1-null individuals. However, the absence of a modulatory effect of polymorphic xenobiotic metabolising enzymes and diet on the development of cancer has been indicated by some epidemiological investigations. Studies of interactions between nutrients and genes may have great potential for exploring mechanisms, identifying susceptible populations/individuals and making practical use of study results to develop preventive strategies beneficial to human health.

Plasma trace element (Se, Zn, Cu) concentrations in maternal and umbilical cord blood in Poland. Relation with birth weight, gestational age, and parity.

Selenium (Se), copper (Cu), and zinc (Zn) concentrations were determined in plasma of 64 mothers at delivery, 58 nonpregnant women, 64 neonates, and 12 infants, aged 2–12 mo. Se and Zn concentrations in mothers at delivery were significantly lower, and Cu higher than in nonpregnant women. Mean Se and Cu concentrations in newborns were statistically lower than those in mothers at delivery, and Zn and Cu concentrations in preterm infants (n=13) were significantly higher than in fullterm infants (n=51). Maternal parity had no significant influence on the distribution of plasma trace element levels. No significant differences were observed in Se and Zn levels in maternal and cord blood plasma according to birth weight, contrary to maternal Cu concentration. Significant correlations were found between maternal and cord blood Se content, and between maternal plasma Cu concentration and birth weight of neonates.

Selenium and glutathione peroxidases in blood of patients with different stages of chronic renal failure.

In patients with chronic renal failure (CRF) Se concentration in blood components is usually lower as compared with healthy controls. One of the five known forms of Se-dependent glutathione peroxidases (GSH-Px), the plasma GSH-Px, is synthesized primarily in the kidney. In CRF patients, plasma GSH-Px activity is reduced and the reduction increases with the progress of the disease. The Se concentration in blood components was measured spectrofluorometrically with 2,3-diaminonaphthalene as complexing reagent. Activities of GSH-Px in red cells and in plasma were assayed by the coupled method with t-butyl hydroperoxide as substrate. The study group consisted of 150 patients in different stages of CRF. The results were compared with the values for 30 healthy subjects. Se concentrations in whole blood and plasma of the entire group of patients were significantly lower (p < 0.01) as compared with the healthy subjects. In the incipient stage, however, the Se levels in all blood components were non-significantly lower. In whole blood and plasma the Se levels gradually decreased, reaching in the end stage values that were lower by 29 to 32% (p < 0.0001) as compared with the control group. Total protein and albumin levels in plasma of patients were significantly lower (p < 0.0001) as compared with healthy subjects and they decreased linearly with the progress of the disease. Positive and highly significant correlations were noted between total plasma protein and plasma Se concentrations (p < 0.0001) as well as between plasma albumin and plasma Se concentrations (p < 0.0001). Red cell GSH-Px activity in the entire group of patients was lower (p < 0.05) than in the control group and did not change significantly with the progress of the disease. In plasma, however, GSH-Px activity of the entire group was lower by 33% (p < 0.0001) as compared with healthy subjects and decreased gradually with increasing renal failure. Highly significant, inverse correlations were seen between creatinine levels and plasma GSH-Px activities (p < 0.0001) as well as between urea nitrogen levels and plasma GSH-Px activities (p < 0.0001) when all stages of the disease were included. In conclusion, patients with CRF exhibit lower Se levels in blood components as compared with healthy subjects. In whole blood and plasma these levels decrease with the progress of the disease. Plasma GSH-Px activity in patients was extremely reduced and it dramatically decreased with the progress of the illness.

Selenium, zinc, and copper concentrations in the blood and milk of lactating women.

The aim of the study was to determine Se, Zn, and Cu concentrations in blood plasma and milk of lactating women from central Poland who were in different stages of lactation and to investigate the relationship between the content of trace elements in mothers’ blood and concentrations of microelements in their milk. Se and Zn concentrations in blood plasma of mothers were the lowest and Cu was the highest on the first 4 d of lactation (colostrum, n=43) and were found to be 34.9±11.8 µg/L, 0.51±0.13 mg/L, and 1.70±0.55 mg/L, respectively. The highest plasma level of Se and Zn and the lowest content of Cu could be observed between d 10 and 30 of lactation (mature milk, n=41), and were found to be 54.3±14.6 µg/L for Se (p<0.001), 0.76±0.20 mg/L for Zn (p<0.001), and 1.03±0.30 mg/L (p<0.001) for Cu.The results of Se, Zn, and Cu determination in breast milk samples demonstrate a pattern of decline in their concentration with advancing stages of lactation. We found out that Se, Zn, and Cu concentrations were the highest in colostrum (n=43) and amounted to 24.8±10.1 µg/L, 8.2±2.8 mg/L, and 0.45±0.11 mg/L, respectively. The content of all determined microelements declined significantly during the time of lactation. Statistically significant linear correlation was found between concentrations of Zn in blood plasma and milk in the first stage of lactation. Weak but statistically significant linear correlations were also found between plasma Se content in plasma and in transitional and mature milk of breast-feeding women.

Detection of infectious agents by polymerase chain reaction in human aortic wall

INTRODUCTION Several studies have been suggested that infectious agents may induce or progress the process of atherosclerosis in humans. In the present study, the samples of visually healthy human aortic wall were examined for the presence of Chlamydia pneumoniae, Mycoplasma pneumoniae, Helicobacter pylori, herpes simplex virus (HSV), and cytomegalovirus (CMV). METHODS Bacterial DNA of C. pneumoniae, M. pneumoniae, and H. pylori and viral DNA of HSV and CMV were analyzed by polymerase chain reaction. The specimens were obtained from 40 patients with atherosclerotic three-vessel stable coronary artery disease referred to surgical revascularization (coronary group) and 20 controls referred to aortic valve replacement (valve group). RESULTS C. pneumoniae was detected in 11 of 40 samples of aorta in coronary group (27.5%) and 5 of 20 in valve group (25%). M. pneumoniae was found in 6 of 40 (15%) and 5 of 20 (25%) samples, and CMV was found in 22 of 40 (55%) and 10 of 20 (50%) samples. The most frequent detected pathogens were H. pylori and HSV. H. pylori was found in 32 of 40 samples of aortic wall in coronary group (80%) and 17 of 20 samples in valve group (85%), whereas HSV was found in 27 of 40 (67.5%) and 17 of 20 (85%) aortic wall specimens. CONCLUSION Results demonstrate that C. pneumoniae, M. pneumoniae, H. pylori, CMV, and HSV can be detected in macroscopically healthy aortic wall of coronary and valve patients in similar frequency, which do not support hypothesis concerning the role of microorganisms in atherosclerosis etiology.

Selenium concentrations and glutathione peroxidase activities in blood of patients before and after allogenic kidney transplantation

In animals and humans, the highest level of selenium (Se) occurs in the kidney. This organ is also the major site of the synthesis of the selenoenzyme glutathione peroxidase (GSH-Px). Decreased Se levels and GSH-Px activities in blood are common symptoms in the advanced stage of chronic renal failure (CRF). Blood samples for Se levels and GSH-Px activities measurements from patients were collected just before transplantation and 3, 7, 14, 30, and 90 d posttransplant. The Se levels in whole blood and plasma of patients before transplantation (79.5 and 64.5 ng/mL, respectively) were lower by 23% and 21%, respectively, as compared with controls (p<0.0001), and 7 d after operation, it further decreased in both components (p<0.01). Fourteen days after surgery, the levels reached the initial values and increased slowly in the later period. Red blood cell GSH-Px activity in patients in the entire period of the study did not differ from the control group. Plasma GSH-Px of patients before the surgery was extremely low (76 U/L) as compared with controls (243 U/L; p<0.0001) but increased rapidly to 115 U/L after 3 d, to 164 U/L after 14 d, and to 208 U/L after 3 mo posttransplant. In CRF patients, after kidney transplantation, plasma GSH-Px activity increased rapidly, approaching, after 3 mo, the values that were close to the normal levels. A negative correlation between creatinine level and plasma GSH-Px activity is observed in patients after kidney transplantation. Monitoring of plasma GSH-Px activity may be a useful additional marker of the transplanted kidney function.

Association between occupational exposure to arsenic and neurological, respiratory and renal effects

Occupational exposure by inhalation in copper smelter is associated with several subclinical health phenomena. The respiratory tract is usually involved in the process of detoxication of inhaled noxious agents which, as arsenic, can act as inductors of oxidative stress (Lantz, R.C., Hays, A.M., 2006. Role of oxidative stress in arsenic-induced toxicity. Drug Metab. Rev. 38, 791-804). It is also known that irritating fumes affect distal bronchioles of non-ciliated, epithelial Clara cells, which secrete anti-inflammatory and immunosuppressive Clara cell protein (CC16) into the respiratory tract. The study group comprised 39 smelters employed at different workplaces in a copper foundry, matched for age and smoking habits with the control group (n=16). Subjective neurological symptoms (SNS), visual evoked potentials (VEP), electroneurographic (EneG) and electroencephalographic (EEG) results were examined in the workers and the relationships between As concentration in the air (As-Air) and urine (As-U) were assessed. Effects of exposure were expressed in terms of biomarkers: CC16 as early pulmonary biomarker and beta(2)-microglobulin (beta(2)M) in urine and serum and retinol binding protein (RBP) as renal markers, measured by sensitive latex immunoassay. The concentrations of arsenic exceeded about two times the Threshold Limit Values (TLV) (0.01 mg/m(3)). The contents of lead did not exceed the TLV (0.05 mg/m(3)). Low CC16 levels in serum (12.1 microg/l) of workers with SNS and VEP symptoms and highest level As-U (x(a) 39.0 microg/l) were noted earliest in relation to occupational time. Moreover, those effects were associated with increased levels of urinary and serum beta(2)M and urinary RBP. Results of our study suggested the initiative key role of oxidative stress in triggering the processes that eventually lead to the subclinical effects of arsenic on the nervous system.

Selenium Supplementation Reduced Oxidative DNA Damage in Adnexectomized BRCA1 Mutations Carriers

Some experimental evidence suggests that BRCA1 plays a role in repair of oxidative DNA damage. Selenium has anticancer properties that are linked with protection against oxidative stress. To assess whether supplementation of BRCA1 mutation carriers with selenium have a beneficial effect concerning oxidative stress/DNA damage in the present double-blinded placebo control study, we determined 8-oxodG level in cellular DNA and urinary excretion of 8-oxodG and 8-oxoGua in the mutation carriers. We found that 8-oxodG level in leukocytes DNA is significantly higher in BRCA1 mutation carriers. In the distinct subpopulation of BRCA1 mutation carriers without symptoms of cancer who underwent adnexectomy and were supplemented with selenium, the level of 8-oxodG in DNA decreased significantly in comparison with the subgroup without supplementation. Simultaneously in the same group, an increase of urinary 8-oxoGua, the product of base excision repair (hOGG1 glycosylase), was observed. Therefore, it is likely that the selenium supplementation of the patients is responsible for the increase of BER enzymes activities, which in turn may result in reduction of oxidative DNA damage. Importantly, in a double-blinded placebo control prospective study, it was shown that in the same patient groups, reduction in cancer incidents was observed. Altogether, these results suggest that BRCA1 deficiency contributes to 8-oxodG accumulation in cellular DNA, which in turn may be a factor responsible for cancer development in women with mutations, and that the risk to developed breast cancer in BRCA1 mutation carriers may be reduced in selenium-supplemented patients who underwent adnexectomy. (Cancer Epidemiol Biomarkers Prev 2009;18(11):2923–8)