Several studies implicated mycotoxins, in endemic kidney disease geographically limited to Balkan region (Balkan endemic nephropathy (BEN)). In Bulgaria, much higher prevalence of ochratoxin A (OTA), exceeding 2 microg/L, was observed in the blood of affected population. OTA is found more often in the urine of people living in BEN-endemic villages. To confirm and quantify exposure to OTA in Vratza district, we followed up OTA intake for 1 month, OTA in blood and urine from healthy (20-30 years old) volunteers, from two villages with high risk for BEN disease. Food samples were collected daily, blood and urine at the beginning of each week. Relations between increasing OTA intake, blood concentration and elimination of OTA in urine have been studied in rats. Average weekly intake of OTA varies from 1.9 to 206 ng/kg body weight, twice tolerable weekly intake recommended by JECFA. OTA blood concentrations are in the same range as previously reported in this region with concentrations reaching 10 microg/L. Weekly OTA food intake is not directly correlated with blood and urine concentrations. Biomarkers of biological effects such as DNA adducts were detected in patients affected by urinary tract tumours (UTT) and in rat study. All these plead for the implication of OTA, in BEN and UTT.
In continuing the effort to provide further evidence for the hypothesis that ochratoxin A might be involved in the aetiology of Balkan endemic nephropathy and the associated urinary system tumours, a survey to determine the occurrence of ochratoxin A in human blood was conducted in affected and unaffected areas of Bulgaria, where both diseases are prevalent. Ochratoxin A, positive samples, were present more often in blood from affected patients and the contamination levels were generally higher.
In the 1950s, a series of publications from Bulgaria, Yugoslavia, and Romania locally described a kidney disease called Balkan Endemic Nephropathy (BEN). In Bulgaria, the exposure of populations to ochratoxin A (OTA) was supported by analysis of individual food items demonstrating a higher prevalence and higher levels of OTA in food from the high-incidence areas of BEN. In this work, food consumption from a series of individuals from two villages of the BEN area during 1 month was followed using the duplicate diet method. Meals consumed by volunteers from both villages showed uneven OTA contents, spreading from below the limit of quantification (<0.07 microg/kg) to 2.6 microg/kg. The average weekly intake of OTA varies from 1.86 to 92.7 ng/kg of body weight. Some of these levels approach the provisional tolerable weekly intake (PTWI) established by the JECFA at 100 ng/kg of body weight. These results confirm previous studies performed in the same area and demonstrate the high exposure of this population to OTA, thus strengthening the hypothesis of the involvement of this mycotoxin in BEN etiology.
Data on the occurrence of endemic nephropathy (EN) and urinary tract and other cancers in an endemic region of Vratza district, Bulgaria, for the years 1965-1974, are presented. In endemic villages a high incidence of urinary tract tumours, affecting in particular the renal pelvis and ureter, closely correlated with the EN incidence and mortality rates. In the villages with high and moderate EN incidences urinary tract tumours are the most common neoplasms. They account for 25% of all tumour sites in males and 30% in females. In hyperendemic villages age-adjusted incidences in EN and urinary tract tumours were 506/10(5) and 104/10(5) in females, and 315/10(5) and 89/10(5) in males respectively. EN mortality in these villages accounted for over 40% of all deaths in females and about 30% in males. Both diseases displayed peculiar geographic clustering. Females and middle-aged persons were most often affected. Urinary tract neoplasms were often multiple and nearly 90% of them originated in the uro-epithelium. In endemic and non-endemic villages of the region studied, the frequency and pattern of non-urinary tract cancers were rather similar, with statistical values close to those of the rural population of Vratza District and Bulgaria as a whole.
No significant differences in terms of TtPD and ORR were observed between the two treatment arms. Treatment-related toxicity was higher in the GET arm.
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