Molka Feki-Tounsi

Cadmium as a possible cause of bladder cancer: a review of accumulated evidence

Bladder cancer is a significant disease, the rates of which have increased over the few last years. However, its etiology remains as yet undefined. Cadmium, a widespread environmental carcinogen that has received considerable interest, presents evidence as a possible cause of bladder cancer. A literature review was conducted from the years 1984–2013 to study the accumulated evidence for cadmium as a possible cause of bladder cancer, including routes of cadmium exposure, accumulation, toxicity, carcinogenicity, and evidence from epidemiological and experimental studies. Special reference is devoted to cadmium nephrotoxicity, which illustrates how cadmium exerts its effects on the transitional epithelium of the urinary tract. Mechanisms of carcinogenesis are discussed. The effects of cadmium on gene expression in urothelial cells exposed to cadmium are also addressed. Despite different methodologies, several epidemiologic and nephrotoxicity studies of cadmium indicate that occupational exposure to cadmium is associated with increased risk of bladder cancer and provide additional evidence that cadmium is a potential toxic element in urothelial cells. In vitro studies provide further evidence that cadmium is involved in urothelial carcinogenesis. Animal studies encounter several problems such as morphology differences between species. Among the complex mechanisms of cadmium carcinogenesis, gene expression deregulation is the subject of recent studies on bladder cadmium-induced carcinogenesis. Further research, however, will be required to promise a better understanding of the mechanisms underlying cadmium carcinogenesis and to establish the precise role of cadmium in this important malignancy.

Trace metal quantification in bladder biopsies from tumoral lesions of Tunisian cancer and controls subjects

The incidence of bladder tumors has been dramatically increasing since the 1970s, possibly as a consequence of ongoing environmental pollution. Previous studies have provided some evidence of an association between cancer and exposure to carcinogenic metals. In order to examine the association between levels of toxic metals in patients with bladder tumors and controls, the amounts of arsenic, cadmium, chromium, and nickel were measured in tumoral lesions and adjacent normal part of the bladder mucosa excised for carcinoma and compared with those in the bladder mucosa of volunteer subjects operated for non-neoplastic diseases. The quantification of metals in tissue was assessed by atomic absorption spectroscopy. In tumoral tissues of the excised bladder mucosa, content of Cr and Ni was significantly low compared to that of adjacent normal tissues and control tissues while that of As and Cd in normal tissues adjacent to the tumor were significantly elevated compared to controls. Though the sample size was small, the present study shows that concentrations of metals such as Cd, Cr, As, and Ni in bladder tissue may be used as a biomarker of exposure. On the basis of the results obtained in this study, high amounts of As and Cd in adjacent normal parts of the bladders with carcinomas compared to controls would strongly suggest possible, individual or synergistic, effects of these pollutants on enzymatic systems, priming an oncogenic pathway.

Cytogenetic damage in the oral mucosa cells of bladder cancer patients exposed to tobacco in Southern Tunisia

Bladder cancer was associated to exposure to several pollutants which can be absorbed, inhaled, or possibly ingested. We analyzed the frequency of micronuclei (MNC) and binucleated cells (BNC) in exfoliated cells of the oral mucosa of 24 bladder cancer (BC) patients and 48 controls residing in Southern Tunisia. An assessment was carried out on the incidence of MNC and BNC in 1,000 cells per individual. The data were analyzed with SPSS, using the chi-square and the Mann-Whitney U test, α = 0.05. The frequency of MN cells in BC cases was 2.5-fold higher, than in the control group (P < 0.001), while the difference for BNC between both groups was not significant. The smoking habits, age, and gender significantly influenced the MN but not the BNC alterations. The results of our study showed significantly increased frequencies of MN but not of BNC in exfoliated oral cells of BC patients associated with the smoking status, sex, and age. This study provides preliminary evidence that the frequency of MN in oral mucosa could be a predictive biomarker for cancers in parts of the body other than the upper aerodigestive tract, such as BC. Further scrupulous investigations are certainly warranted in order to implement this assay as a routine test in the planning and validation of cancer surveillance and prevention programs.

Blood Cr and Ni in Bladder Cancer and Prostate Adenoma Patients

The established risk factors for bladder cancer (BC), which has been increasing in recent years worldwide and in Tunisia (Parkin et al. in Cancer J Clin, 55:74–108, 2005), could not explain the exceptionally high incidence of cancer by itself, suggesting that additional risk factors might be involved.