Oxidative Stress and Antioxidant Status in Nigerian E-waste Workers: A Cancer Risk Predictive Study.

Introduction: In Africa, Nigeria has been reported as the largest destination for unregulated volume of electronic waste (e-waste). Currently, e-waste management practices in Nigeria remain completely primitive, taking place essentially in the informal sector. Recent report indicates that the majority (88.8%) of Nigerian e-waste workers have exposure burden of ≥6 hours per day; ≥6 days per week, and reportedly worked without personal protective devices. These crude management practices enhance the workers’ exposure to electronic waste borne toxic and carcinogenic metals and chemicals through almost all body cavities. Objective: Concisely, this study aimed at evaluating the status of enzymatic and non-enzymatic oxidative stress biomarkers as cancer risk indices in Nigerians occupationally exposed to e-waste. Methods: Serum levels of malondialdehyde (MDA), uric acid (UA), albumin (ALB), total bilirubin (TBil) and conjugated bilirubin (Cbil.)] and activities of enzymatic antioxidants [glutathione reductase (Gr), catalase (Cat), superoxide dismutase (SOD) and glutathione peroxidase (GPx)] were determined in Nigerian e-waste workers (n=63) and in age-matched unexposed participants (n=41), using standard colorimetric methods. Results: Significantly elevated lipid peroxidation and raised uric acid levels were indicated in e-waste workers. Further to this, CAT, SOD and GPx were significantly reduced in e-waste workers compared with the unexposed human population. Comparatively different observations were not registered in the activity of GR and levels of ALB, TBil. and CBil. between exposed and unexposed participants. Conclusion: This study provides evidence that the oxidative stress observed in the studied population could be associated with occupational exposure to e-waste chemicals and may be a predictive mechanism for chemical carcinogenesis in Nigerians involved in primitive e-waste management.

The inhibition of skin tumor growth in Galecit n-3-deficient mice / 实用肿瘤学杂志

Objective To observe the effect of Galectin -3 gene knock out to the mouse skin tumor growth and discuss the mechanism of inhibition of the mouse cutaneous tumor induced by 12 -o -tetrade-canoylphorbol-13-acetate which caused by Galectin -3 knock out.Methods The DMBA +TPA multi-step induced skin tumor in mice model were used to establish the skin cancer model .The control group was the same age wild type mice .We observed the inhibition of the mouse tumor growth by Galectin -3 knock out .In situ tumor cells were collected and cultured on soft agar for colony formation assay .The side population of the situ cancer cells was analyzed quantitatively by flow cytometry .Results 1.Compared with wild type mice group(group A), Galectin-3 knock out mice group ( group B) displayed a significant delay of the appearance of tumor .The tumor incidence and the average number of tumor per mice between group A and group B had obvious difference ( P<0.01).2.In vitro,data of soft agar colony formation assay showed that colony formation rate in group A are signif -icantly higher than group B(P<0.01).3.The collection and separation of A and B group in situ tumor cells ,u-sing flow cytometry instrument for in situ tumor cell side population quantitative analysis ,group A compared with group B had obvious difference(P<0.01).Conclusion The knock out of the Galectin -3 gene reduces the skin cancer stem cells ,inhibits tumor cell proliferation ,depresses chemical carcinogenesis of mice skin .Galectin-3 gene may become the new target for skin cancer chemotherapy .

Oral submucous fibrosis as a precursor of malignancy - a case report

Oral submucous fibrosis (OSF) is a high risk precancerous condition predominantly occurs in Indians and other population of the Indian subcontinent with certain oral habits. Betel quid (BQ) chewing is a popular oral habit with potential links to the occurrence of oral cancer. In patients with submucous fibrosis, the oral epithelium becomes atrophic and thereby becomes more vulnerable to carcinogens. Since the ingredients of BQ, tobacco are crucial for tumour initiation, promotion and progression, exposure to these toxicants simultaneously has been shown to markedly potentiate the oral cancer incidence in OSF patients. The rate of malignant transformation of OSF has been estimated to be 4.5%. Most cases with malignant transformation in OSF had occurred gradually over a long period of time.

Efeitos da Ginkgo biloba sobre o desenvolvimento e o crescimento de neoplasias de mama em ratas da linhagem Sprague-Dawley / Effects of Ginkgo biloba on the development and growth of breast cancers in wistar female Sprague-Dawley

O presente estudo teve como objetivo avaliar as propriedades quimioprotetoras e terapêuticas do extrato de Ginkgo biloba (EGb) sobre o desenvolvimento de lesões mamárias neoplásicas induzidas pela dimetil(a)benzoantraceno (DMBA) em ratas da linhagem Sprague-Dawley. No artigo 1 (Quimioprevenção), os animais foram divididos aleatoriamente em quatro grupos experimentais, sendo dois grupos controles (Positivo e Negativo) e dois grupos teste. Aos 51 dias de idade, as fêmeas receberão por gavagem (i..g) dose única de 60mg/kg de DMBA ou de óleo de Canola (veiculo da DMBA) e receberam ou não a substância teste (EGb) misturada à ração basal nas concentrações de 0,1 e 0,2%. Ao final da 18ª semana, todos os animais foram eutanasiados na câmara de CO2 e foram coletados ovários, úteros e tumores mamários, fixados em formalina tamponada 10% e processados histologicamente para as análises histopatológicas. Também foram coletadas e congeladas (nitrogênio líquido) amostras dos tumores mamários para a análise dos níveis protéicos de bax, bcl-2 e do receptor de estrógenoalfa (RE-a). O tratamento com EGb nas duas concentrações não modificou a latência, incidência, multiplicidade e tipos histológicos das neoplasias mamárias e não foi capaz de impedir o crescimento e malignidade dessas neoplasias. Além disso, o EGb não alterou os níveis das proteínas apoptóticas bax, bcl-2 e do RE-a nas neoplasias mamárias induzidas pela DMBA. No artigo 2 (Terapêutica), todos os animais foram iniciados pela DMBA (80mg/kg; i.g.). A partir do momento que apresentaram tumores mamários palpáveis, os animais foram divididos aleatoriamente em quatro grupos experimentais recebendo ou não o tratamento com Tamoxifeno (TAM) (10mg/kg; i.g.) e/ou EGb (50-100mg/kg; i.p.) durante 28 dias consecutivos...

The present study was designed to investigate the chemopreventive and therapeutic properties of Ginkgo biloba extract (EGb) on 7,12-dimethylbenz( o)anthracene (DMBA)-induced mammary tumors in female Sprague-Dawley rats (SD). In the manuscript 1 (Chemoprevention), the experimental design comprised of four experimental groups, including two control groups (positive e negative) and two test-groups. The 51 days-old female SD rats received a single dose of DMBA (60 mg/kg, i.g.) or a single administration of Canola oil (DMBA vehicle) and were fed with basal diet or EGb supplemented diet at 0,1 or 0,2 %. At 18th week, all animals were euthanized in CO2 atmosphere, the ovaries, uterus and mammary tumors were fixed in 10% phosphate-buffered formalin and processed in order to provide 5-μm thick paraffin sections for histological analysis. Also, tumor samples were frozen in liquid nitrogen for the analysis of bax, bcl-2 and estrogen receptor alpha (ER-a) protein expression by Western blot. The EGb intake did not alter the latency, incidence, multiplicity and histological pattern, neither the growth and malignancy of the mammary tumors. Besides, the treatment with EGb did not modify the bax, bcl-2 and estrogen receptor alpha (ER-a) expression in the mammary neoplasm induced by DMBA. In the manuscript 2 (Therapy), the experimental design comprised of four experimental groups. Female SD rats bearing palpable mammary neoplasms induced by DMBA (80 mg/kg b.wt., i.g.) received (G1) TAM (10 mg/kg b.wt., i.g.); (G2 and G3) TAM + EGb (50 or 100 mg/Kg b.wt., i.p.) or (G4) EGb (100 mg/kg b.wt., i.p.) during 28 days...

The role of thalidomide on cachexia during experimental skin carcinogenesis in mice

We investigated the effect of thalidomide on cachexia and TNF-α serum levels during experimental skin carcinogenesis in mice. Female mice were divided into four groups: 1) DMBA (dissolved in acetone) induced tumorigenesis; 2) DMBA and Thalidomide (dissolved in DMSO); 3) DMBA and DMSO; and 4) Acetone. Body weight was measured once a week. Euthanasia was performed 14 weeks later, when blood was collected for the dosage of TNF-α serum levels. Mice with DMBA induced tumorigenesis had a significant loss of body weight when compared to acetone treated animals, starting at the third week and lasting the whole experiment. But there was no difference among Thalidomide treated and the others DMBA control animals, regarding body weight. High TNF-α serum levels were associated with the development of cachexia in mice during the process of experimental skin tumorigenesis. However, there was not a significant difference in the TNF-α serum levels when compared control mice and thalidomide treated mice. These results suggest that thalidomide does not interfere with skin tumorigenesis, cachexia and serum TNF-α levels in Balb/C mice. In addition, high TNF-α serum levels are associated to weight loss during experimental carcinogenesis.

Chemical carcinogenesis

The use of chemical compounds benefits society in a number of ways. Pesticides, for instance, enable foodstuffs to be produced in sufficient quantities to satisfy the needs of millions of people, a condition that has led to an increase in levels of life expectancy. Yet, at times, these benefits are offset by certain disadvantages, notably the toxic side effects of the chemical compounds used. Exposure to these compounds can have varying effects, ranging from instant death to a gradual process of chemical carcinogenesis. There are three stages involved in chemical carcinogenesis. These are defined as initiation, promotion and progression. Each of these stages is characterised by morphological and biochemical modifications and result from genetic and/or epigenetic alterations. These genetic modifications include: mutations in genes that control cell proliferation, cell death and DNA repair - i.e. mutations in proto-oncogenes and tumour suppressing genes. The epigenetic factors, also considered as being non-genetic in character, can also contribute to carcinogenesis via epigenetic mechanisms which silence gene expression. The control of responses to carcinogenesis through the application of several chemical, biochemical and biological techniques facilitates the identification of those basic mechanisms involved in neoplasic development. Experimental assays with laboratory animals, epidemiological studies and quick tests enable the identification of carcinogenic compounds, the dissection of many aspects of carcinogenesis, and the establishment of effective strategies to prevent the cancer which results from exposure to chemicals.

A sociedade obtém numerosos benefícios da utilização de compostos químicos. A aplicação dos pesticidas, por exemplo, permitiu obter alimento em quantidade suficiente para satisfazer as necessidades alimentares de milhões de pessoas, condição relacionada com o aumento da esperança de vida. Os benefícios estão, por vezes associados a desvantagens, os efeitos resultantes da exposição a compostos químicos enquadram-se entre a morte imediata e um longo processo de carcinogênese química. A carcinogênese química inclui três etapas definidas como iniciação, promoção e progressão. Cada uma delas caracteriza-se por transformações morfológicas e bioquímicas, e resulta de alterações genéticas e/ou epigenéticas. No grupo das alterações genéticas incluem-se mutações nos genes que controlam a proliferação celular, a morte celular e a reparação do DNA - i.e. mutações nos proto-oncogenes e genes supressores de tumor. Os fatores epigenéticos, também considerados como caracteres não genéticos, podem contribuir para a carcinogênese por mecanismos de silenciamento gênico. A utilização de diferentes metodologias possibilita o reconhecimento e a compreensão dos mecanismos básicos envolvidos no desenvolvimento do cancro. Ensaios experimentais comanimais de laboratório, estudos epidemiológicos e alguns testes rápidos permitem identificar compostos carcinogênicos, analisar os eventos envolvidos na carcinogênese e estabelecer estratégias para prevenir a exposição a estes agentes.

Chemoprevention of Mammary, Cervix and Nervous system Carcinogenesis in Animals using Cultured Panax ginseng Drugs and Preliminary Clinical Trials in Patients with Precancerous Lesions of the Esophagus and Endometrium

The anticarcinogenic effects and mechanisms of the biotechnological drugs of Panax ginseng C.A. Meyer cultivated in Russia, bioginseng, panaxel and panaxel- 5, were studied. Bioginseng was produced from a tissue culture of ginseng root cultured on standard medium, whereas panaxel and panaxel-5 were produced from ginseng tissue root cultures using standard mediums enriched with 2-carboxyethylgermanium sesquioxide and 1-hydroxygermatran-monohydrate respectively. All three ginseng drugs inhibited the development of mammary tumors induced by intramammary injections of N-methyl-N-nitrosourea (MNU) in rats, the development of the brain and spinal cord tumors induced by transplacental administration of N-ethyl-N-nitrosourea (ENU) in rats, and the development of uterine, cervical and vaginal tumors induced by intravaginal applications of 7,12-dimethylbenz(a)anthracene (DMBA) in mice. The ginseng drugs induced the cytotoxic activity of macrophages in mice, enhanced T-lymphocyte rosette formation in guinea pigs exposed to cyclophosphamide, and stimulated the production of thyroid hormones in rats. These mechanisms may contribute to the anticarcinogenic action of the ginseng drugs. The organic germanium compounds present in panaxel and panaxel-5 did not potentiate the anticarcinogenic or immuno- stimulatory effects as much as biogeinseng. Preliminary clinical trials with panaxel and bioginseng were carried out in patients with precancerous lesions of the esophagus and endometrium. Panaxel was found to have a strong therapeutic effect in patients suffering from chronic erosive esophagitis. Bioginseng induced the regression of adenomatous-cystic hyperplasia of the endometrium in some patients. Thus, we conclude that the drugs of ginseng appear to hold considerable promise for future cancer chemoprevention.

Effects of Green Tea Infusion on the Preneoplastic Lesions and Peroxidation in Rat Hepatocarcinogenesis / 대한지역사회영양학회지

The effect of green tea drinking on the hepatocellular chemical cacinogenesis have been studied. Placental glutathione S-transferase(GST-P) positive foci area in a liver tissue, contents of thiobarbituric acid reactive substances(TBARS), total cytochrome P450 and glucose 6-phospphatase(G6P) activity in hepatic microsomes were investigated. Weaning Sprague-Dawley male rats were fed AIN-76A diet with deionized water or green tea infusion, Rats of CTR and CTR+ groups were provided deionized water while GTI and GTI+ groups were provided green tea instead of deionized water for the entire experimental period of 13weeks. Rats of GTP and GTP + groups had deionized water for the first 6 weeks and switched to green tea for the last 7weeks of the experimental period. CTR+, GTI +, and GTP + groups were carcinogen treated groups, Diethylnitrosamine(DEN) was injected as a single dose of 200 mg/kg body weight intraperitoneally after 4 weeks of feeding. 2-Acetyla-minofluorene(AAF) was used as a carcinogen proliferater and suppled in the diets of carcinogen treated rats as 0.02% content for the last 6weeks starting from 2weeks after DEN injection. Rats were sacrificed after 13week weeks of feeding. The area and number of GST-P positive foci detected in carcinogen treated rats were decreased by green tea ingestion but when timing and duration of green tea ingestion was delayed after promotion period as in GTP + group, GST-P positive foci were not decreased as much as in GTI+ group. TBARS contents of carcinogen treated rats decreased by 13weeks of green tea ingestion but GTP groups did not show statiscally significant differences. G6P activities tended to decrease by carcinogen treatment but changes were not statiscally significant by green tea ingestion. Total cytochrome P450 contents were increased by carcinogen treatment. Thirteen weeks of green tea ingestion (GTI) also increased to total cytochrome P450 contents while 7weeks of green tea ingestion(GTP) did show any effects. These results suggest that green tea has suppressive effects on hepatocellular chemical carcinogenesis probably through the activities of antioxidant compounds.

The Changes of Histopathology, Proliferation Activity, and Nuclear DNA Content N-butyl-N-(4-hydroxybuty1) Nitrosamine(BBN) Induced Bladder Cancer in Rats / 대한비뇨기과학회지

To evaluate the process of tumor progression in chemical carcinogenesis of the bladder cancer. 0.05% BBN was administered to female Wistar rats for 12 weeks. The rats were divided into six groups and sacrificed every or every two weeks from the 12th to the 20th weeks. Cellular touch imprints of urinary bladder for DNA content analysis by image analyzer and mean AgNORs count per nucleus were performed immediately after sacrifice. Thereafter, the urinary bladder was embedded in paraffin for histopathological examination.On histopathological findings, simple hyperplasia was found in all cases after 12 weeks therapy of BBN. Atypical hyperplasia of the bladder, indicative of a precancerous state, was found in 88.9% of the 12 weeks group, 83.3% of the 13 weeks and in all cases after 14 weeks therapy of the BBN. Bladder cancer was found in 33.3% of the 13 weeks, 55.6% of the 14 weeks, and 100% of the above 16 weeks therapy group. The nuclear DNA content of 21 cases of atypical hyperplasia was diploid in 19 cases(91.5%) and aneuploid in 2 cases(9.5%). DNA aneuploidy was found in 18 cases(66.7%) among the 27 cases of the cancer group. Mean AgNORs count per nucleus and proliferation index by flowcytometry were higher in atypical hyperplasia and cancer group than these of simple hyperplasia and control group, but those differences according to histologic type were not statistically significant. And there was statistically significant correlation between proliferation index and mean AgNORs count per nucleus(r=0.57, p<0.05). These data suggest that the change of nuclear DNA content might occur during the early phase of the carcinogenesis in BBN-induced bladder cancer of rats.