Ochratoxin A-related DNA adducts in urinary tract tumours of Bulgarian subjects.

Ochratoxin A (OTA), a natural contaminant of mouldy food and feed, is suspected of being one of the etiological agents responsible for Balkan endemic nephropathy (BEN) and the associated urinary tract tumours. We have previously shown that ochratoxin A is genotoxic as expressed by DNA single-strand breaks. DNA-OTA adducts have been detected in various mouse organs after ochratoxin A treatment. Tumorous tissues from three kidneys and five bladders of Bulgarian patients undergoing surgery for cancer and from three non-malignant kidneys collected from French subjects were analysed for DNA adducts. Several adducts with the same RF values as those obtained from mouse kidney after treatment with OTA (one major and some minor adducts) were detected, mainly in kidney but also in bladder tissues from Bulgaria. No adducts were detected in French kidney tissues. These results provide new evidence of the possible role of OTA in the development of tumours of the urinary tract in Bulgaria.

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 -- 79.8 and 74.9; in a slow growing and metastasizing melanotic melanoma -- 67.7; in undifferentiated amelanotic and depigmented melanomas with very fat growth -- 72.8 and 77.4. Therefore no consistent relationship has emerged between histogenesis, growth rate, differentiation and metastases of the studied neoplasms from one side and their LDH isozyme pattern -- on the other.

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. This was followed by a complete disappearance of LDH 1,2,3. In the tumors appearing after re-inoculation of cultured cells, re-emergence of the patterns seen in the original tumors was noted. The mechanism of the observed changes remains hypothetical although an adaptive re-arrangement of gene activity controlling the production of M and H subunits and/or in vitro selection of clones with higher M/H ratio is postulated.

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. In the epidermis from new born, 25-day-old (growing stage of the hairs) and 60 to 80-day-old (resting stage of the hairs) animals a relative increase of the H subunits is striking. These results reveal a foetal-like pattern of LDH isozymes in regenerating and tumorous epidermis, as has been observed in other isozymes and in other tissues.

Tumors and hyperplastic lesions in Syrian hamsters following transplacental and neonatal treatment with cigarette smoke condensate.

Cigarette smoke condensate (CSC) in olive oil was injected into outbred Syrian hamsters: in adults i.p. on the 10th--14th days of gestation, total dose 1.5--2.5 mg/g b.w.; in 12 to 14-days-old animals s.c., total dose 0.5--1.5 mg/animal. Following 15--25 months of observation benign and malignant neoplasms of various location were found in 2/58 (3.4%) females, treated during pregnancy; in 17/51 (33.3%) of their transplacentally exposed offsprings; in 5/53 (9.4%) of neonatally treated hamsters. In the last two groups females were more affected than males. Most frequently occurred tumors of adrenal glands, pancreas, female sex organs, and liver. No tumors appeared in controls, either untreated or injected with olive oil. In addition, hyperplastic lesions, in particular multiple liver cysts and cholangiomatosis were also observed, mainly in animals exposed transplacentally and as neonates.

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 16.8 for males and 14.9 for females in case of kidney tumors and as 7.1 in males and 10.2 for females in case of urinary bladder tumors. On village group basis a very close correlation between mortality rates from urinary system tumors and EN incidence rates has been disclosed although endemic and non-endemic villages are neighbouring and are very similar in ecological and cultural terms.

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. 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.