Balkan endemic nephropathy: role of ochratoxins A through biomarkers.

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.

Analysis of ochratoxin A in foods consumed by inhabitants from an area with balkan endemic nephropathy: a 1 month follow-up study.

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.

Balkan endemic nephropathy and associated urinary tract tumours: a review on aetiological causes and the potential role of mycotoxins.

A series of publications in the 1950s described a kidney disease in Bulgaria, the former Yugoslavia and Romania that became known as Balkan endemic nephropathy (BEN). The disease was qualified by World Health Organisation (WHO) experts as 'progressive and very gradually developing renal failure with insidious onset..

Experimental mycotoxic nephropathy in pigs provoked by a diet containing ochratoxin A and penicillic acid.

Mycotoxic nephropathy was induced in 18 young pigs by diets contaminated with strains of Aspergillus ochraceus containing ochratoxin A (OTA) and penicillic acid (PA) at levels corresponding to those naturally encountered in animal feeds in Bulgaria. Haematological and biochemical parameters, as well as the morphological and ultrastructural changes in various internal organs, and especially in the kidneys, were examined at different stages of development of the disease. A mottled surface of the kidneys was only seen in pigs exposed to a mouldy diet containing 180 ppb OTA for 3 months, but microscopic lesions, as well as changes in various haematological and biochemical parameters, were observed in all groups exposed to the same mouldy diet containing only 90 or 180 ppb OTA.

Citrinin in the diet of young and healthy persons living in balkan endemic nephropathy areas.

The dietary citrinin (CT) intake of 19 persons living in highrisk "Balkan Endemic Nephropathy" areas in Bulgaria was studied. Over 4 weeks, volunteers collected aliquots of their daily meals. Weekly samples were homogenized and analysed for CT by enzyme immunoassay (detection limit: 1ng/g).

Formation of DNA adducts in tissues of mouse progeny through transplacental contamination and/or lactation after administration of a single dose of ochratoxin A to the pregnant mother.

Ochratoxin A (OTA) is a mycotoxin which has been detected in foods of plant origin, in edible animal tissues, and in human sera, urine, and milk in many countries. OTA is nephrotoxic and carcinogenic in mice and rats and is suspected to play a key role in the etiology of Balkan endemic nephropathy and/or associated urinary tract tumors. In the present study, some early signs of genetic impairment, including the presence of DNA adducts in target tissues from the progeny of mice after administration of a single OTA dose during late pregnancy, have been investigated.

Ochratoxin A and other mycotoxins in cereals from an area of Balkan endemic nephropathy and urinary tract tumours in Bulgaria.

The etiology of Balkan endemic nephropathy and urinary tract tumours in the rural population of the endemic regions remains unknown. As one hypothesis involves mycotoxins, a survey was carried out to investigate the possible involvement of the nephrotoxic mycotoxins ochratoxin A and citrinin. Recently, this survey was extended to screening for the presence of other mycotoxins--aflatoxins, citrinin, sterigmatocystin and zearalenone.

Concentrations of ochratoxin A in the urine of endemic nephropathy patients and controls in Bulgaria: lack of detection of 4-hydroxyochratoxin A.

Ochratoxin A has been detected more frequently and at higher levels as a contaminant in staple food consumed by subjects affected by Balkan endemic nephropathy or urinary tract tumours in the Vratza district (Bulgaria) than in samples from control populations in and outside the endemic area. Serum from patients with Balkan endemic nephropathy also contained ochratoxin A more frequently and at higher levels than serum from controls. Metabolic phenotyping of subjects in the Vratza district with debrisoquine revealed a preponderance of extensive metabolizers among subjects at high risk for Balkan endemic nephropathy.

Ochratoxin A in human blood in relation to Balkan endemic nephropathy and urinary tract tumours in Bulgaria.

Ochratoxin A is suspected of being one of the etiological agents responsible for Balkan endemic nephropathy and the associated urinary tract tumours. Contamination of cereals by this mycotoxin has been found to be more frequent in areas of endemic nephropathy than in areas where the disease is absent. As ochratoxin A binds to serum albumin, it should be detectable in biological fluids from exposed populations.

Induction of characteristic chromosomal aberrations, particularly X-trisomy, in cultured human lymphocytes treated by ochratoxin A, a mycotoxin implicated in Balkan endemic nephropathy.

Ochratoxin A (OA), a mycotoxin which induces nephropathy and kidney tumours in rats and mice, is a contaminant of food consumed by a population with a high incidence of endemic nephropathy (EN). It was therefore tested in vitro for its ability to induce chromosomal aberrations in human peripheral lymphocytes in a small number of subjects, in the presence or absence of a kidney microsomal metabolic activation system. OA was found to induce aberrations on X chromosomes of similar types to those previously detected in lymphocytes from patients suffering from endemic nephropathy.

Ochratoxin A in human blood in relation to Balkan endemic nephropathy and urinary system tumours in Bulgaria.

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.

Ochratoxin A contamination of cereals in an area of high incidence of Balkan endemic nephropathy in Bulgaria.

In an effort to provide further evidence for the hypothesis that a mycotoxin is involved in the aetiology of Balkan endemic nephropathy and that the latter is associated with the occurrence of urinary system tumours, a survey was made of ochratoxin A contamination of cereal samples from an area of Bulgaria where both endemic nephropathy and urinary system tumours are prevalent and from non-endemic areas. In all, 130 samples of beans, maize and wheat flour were analysed. Ochratoxin A levels were 16.

LDH isozymes in transplantable hamster tumours with different histogenesis and differentiation.

LDH isozymes were assayed by polyacrylamide gel electrophoresis in 6 long-term transplantable skin tumours in Syrian hamsters. The percentages of the M-subunits were as follows: in a slow growing fibrosarcoma with abortive differentiation and producing lung metastases -- 63.3; in two well differentiated squamous cell carcinomas with moderate growth -- 79.

LDH isoenzymes in cell cultures from transplantable hamster tumors with dissimilar histogenesis and differentiation.

LDH isoenzymes were assayed by acrylamide disc electrophoresis in the following material: (a) cells from 4 transplantable hamster tumors; (b) cells from the same tumors cultured for 0, 4, 12 or 24 h as well as for 3, 7, 12 or 26 days; (c) tumors obtained after re-inoculation of cells cultured for 26 days. During the first days of culture, the cells retained LDH patterns similar to those of tumors in vivo. Then a progressive increase in the M/H ratio was observed in all cultures.

LDH isozymes in epidermis and skin carcinoma in hamsters.

Lactate dehydrogeanse (LDH) isozymes in the epidermis and in transplantable epidermal carcinoma from Syrian hamsters were studied by polyacrilamide electrophoresis. A 5-band pattern with occasional loss of 1--2 anode fractions in certain tumor samples is typical. In the epidermis of 14 to 15-day-old foetuses, in the regenerating epidermis, and in tumor cells cathode of M subunits predominate, in particular the fifth fraction in the last two cases.

Familial aggregation of urinary system tumors in a region with endemic nephropathy.

In hyperendemic villages in the Vratza district of Bulgaria, 193 patients with urinary system tumors (UST) were diagnosed during 1965 to 1976. A tendency towards familial aggregation was revealed when the patients were compared with two groups of controls, namely, patients with tumors other than UST and healthy persons. Each control group consisted of 193 persons matched by sex, age, and place of birth.

Epidemiologic data for environmental determination of urinary system tumours and nephropathy in an endemic region.

One hundred and thirty-eight patients diagnosed for urinary system tumours (UST), 714 patients with endemic nephropathy (EN) and 55 cases of UST and EN combined, all from endemic villages of Vratza district, Bulgaria were investigated for their familial pattern and time of diagnosis compared with the age at diagnosis. There were 144 spouses among these patients and nearly half of them came from non-endemic families and villages. The familial pattern followed the size of the population found to be at greater risk, i.

[Malignant tumors in a region of endemic nephropathy].

In villages with endemic nephropathy (EN) high incidence and mortality rates of some urinary system tumors are reported. Age-adjusted incidences of renal pelvic and ureteral neoplasms were 46/10(5) in females and 27/10(5) in males; for urinary bladder tumors these figures were 16/10(5) and 35/10(5). The frequency of parenchymal kidney tumors was similar to that reported for the country as a whole.

Families with multiple cases of urinary system tumors: brief communication.

A study of three families living in villages with endemic nephropathy (EN) in Vratza district, Bulgaria, revealed 9 members with urinary system tumors (UST), 7 with UST and EN, and 7 with EN. Most cases were registered from 1962 to 1976. The predominant form was transitional cell neoplasms of the kidney pelvis and ureter in patients 40-60 years old.

Geographic correlation between the occurrence of endemic nephropathy and urinary tract tumours in vratza district, Bulgaria.

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.

Cancer mortality in a region with endemic nephropathy.

Cancer mortality in endemic and non-endemic villages from a region with endemic nephropathy (EN) of Vratza district, Bulgaria has been compared for the period 1965--1974. The total and for all cancer sites mortality rates in all studied villages were comparable to European and world standards except a very high mortality from tumors of urinary organs in the endemic villages. Age-adjusted to world population rates/10(5) population in hyperendemic villages have been estimated as 16.