8-hydroxy-2--deoxyguanosine and Schistosomiasis-haematobia

To investigate whether mutant stem cells participate in inflammation-related carcinogenesis, we performed immunohistochemical analysis to examine nitrative and oxidative DNA lesions (8-nitroguanine and 8-oxodG) and a stem cell marker Oct3/4 in bladder tissues obtained from cystitis and bladder cancer patients infected with Schistosomahaematobium (S. haematobium). We also detected the expression of nuclear factor-κB (NF-κB) and inducible nitric oxide synthase (iNOS), which lead to 8-nitroguanine formation. The staining intensity of 8-nitroguanine and 8-oxodG was significantly higher in bladder cancer and cystitis tissues than in normal tissues. iNOS expression was colocalized with NF-κB in 8-nitroguanine-positive tumor cells from bladder cancer patients. Oct3/4 expression was significantly increased in cells from S. haematobium-associated bladder cancer tissues in comparison to normal bladder and cancer tissues without infection. Oct3/4 was also expressed in epithelial cells of cystitis patients. Moreover, 8-nitroguanine was formed in Oct3/4-positive stem cells in S. haematobium-associated cystitis and cancer tissues. In conclusion, inflammation by S.haematobium infection may increase the number of mutant stem cells, in which iNOS-dependent DNA damage occurs via NF-κB activation, leading to tumor development.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Cell Transformation, Neoplastic; Cystitis; Deoxyguanosine; DNA Damage; Guanine; Humans; Neoplastic Stem Cells; NF-kappa B; Nitric Oxide Synthase Type II; Octamer Transcription Factor-3; Schistosoma haematobium; Schistosomiasis haematobia; Urinary Bladder Neoplasms

To cast light on mechanisms underlying development of urothelial carcinomas (UCs) of the urinary bladder associated with Schistosomiasis, we immunohistochemically analyzed the relationship between oxidative stress markers, DNA single strand breaks (ssDNA) which could also measure the levels of base damage and apoptosis in DNA, and expression of DNA repair genes with levels of nitric oxide synthases in bladder carcinomas of Egyptian patients with or without Schistosoma hematobium infection. Marked elevation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels was found in squamous cell carcinomas and UCs associated with Schistosomiasis when compared with non-Schistosomal carcinomas. This was accompanied by strong over expression of the DNA-repair genes, 8-oxoguanine-DNA-glycosylase and apurinic/apyrimidinic endonuclease, as well as increased formation levels of ssDNA. Expression levels of inducible nitric oxide synthase (iNOS) which is known to be indirectly related to oxidative stress was higher in Schistosomal than in the non-Schistosomal carcinomas. However, expression of endothelial nitric oxide synthase was slightly stronger in non-Schistosomal than in the Schistosomal carcinomas. In conclusion, these findings suggest a strong correlation between Schistosoma haematobium infection and increased levels of oxidative stress accompanied by a continuous DNA damage and repair in UCs, all directly correlating with elevated iNOS.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Biomarkers; Biomarkers, Tumor; Carcinoma; Carcinoma, Squamous Cell; Deoxyguanosine; DNA Damage; DNA Repair; Egypt; Female; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Male; Middle Aged; Neoplasm Staging; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Oxidative Stress; Schistosomiasis haematobia; Up-Regulation; Urinary Bladder Neoplasms; Urothelium

Eighty adult male hamsters were used in this study, 20 of them were divided equally into a noninfected, nontreated control group and chronic lead exposed groups, which were given lead acetate intraperitoneally, dissolved in distilled water, 2 mg/kg/day for seven weeks. Then, two experiments were carried out on the remaining animals. Each experiment included 30 animals and was divided equally into three groups. Experiment A was carried out on the following groups: Schistosoma mansoni infected group, S. mansoni infected and chronic lead exposed group and S. mansoni infected, chronic lead exposed and 'Antox' treated group. Experiment B was done following the same design except that infection was carried out using Schistosoma haematobium cercaria. Chronic lead exposure of Schistosoma infected groups showed significant reductions in worm burden, tissue egg load and ova excretion in stool, liver and intestine. Compared with the control group, there were insignificant increases in serum and hepatic glutathione and malondialdehyde levels and a significant increase in hepatic 8-oxodeoxyguanosine phosphate (8-Ox-Dg) levels in Schistosoma infected groups. However, there was a significant increase in hepatic and blood lead levels, oxidative stress parameters and in the hepatic 8-Ox-Dg level in Schistosoma infected and chronic lead exposed groups as compared with their corresponding Schistosoma only infected groups. This study revealed a significant reduction in oxidative stress parameters as well as in blood and hepatic lead levels and in hepatic 8-Ox-Dg levels after giving Antox to the Schistosoma infected and chronic lead exposed groups. However, Antox increased insignificantly all the parasitological parameters studied in the Schistosoma infected and chronic lead exposed groups.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antioxidants; Cricetinae; Deoxyguanosine; Disease Models, Animal; Drug Antagonism; Feces; Glutathione; Intestinal Mucosa; Intestines; Lead Poisoning; Liver; Male; Malondialdehyde; Oxidative Stress; Parasite Egg Count; Schistosoma haematobium; Schistosoma mansoni; Schistosomiasis haematobia; Schistosomiasis mansoni