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Biomedical subjects

J Chowaniec

Publications and source records attributed to J Chowaniec.

7 recordsLinked to original sources
PubMed1992

Evaluation of the actions and interactions of retinoic acid and epidermal growth factor on transformed urothelial cells in culture: implications for the use of retinoid therapy in the treatment of bladder cancer patients.

The effects and interactions were investigated of the two growth regulatory molecules alltrans retinoic acid (RA), and epidermal growth factor (EGF) on the in vitro expression by bladder cancer cell lines of the transformed phenotype (anchorage-independent growth in soft agar). When tested individually, the two molecules had opposite effects: RA (10(-11) to 10(-5) M) caused a dose-related reduction in anchorage-independent growth, whereas EGF (0.1 to 50 ng/ml) caused a dose-dependent increase. These effects were observed with both cell lines tested: RT112, a human papillary, non-metastatic bladder cancer cell line and RU-CL2, a rat metastatic bladder carcinoma cell line. When the effect of EGF (2.5 ng/ml) was tested against the growth inhibition produced by a range of doses of RA, EGF stimulated growth and reduced the degree of inhibition produced by RA at all dose levels. Conversely, a single dose of 10(-8) M RA tested against a range of EGF concentrations reduced the dose-related EGF-induced increase in anchorage-independent growth. The two cell lines responded similarly to those combinations of RA and EGF in vitro, regardless of their different biological potentials in vivo. These experiments provide no evidence that RA potentiates EGF-induced growth, as has been observed by others using mesenchymal cells. RA could, therefore, theoretically be used to inhibit or delay bladder tumour recurrences. Trials would show whether oral doses of RA, or of synthetic retinoids metabolized to RA, would reach therapeutic levels and be chemopreventive in bladder cancer patients.

Animals↗
PubMed1979

Response of the rat to saccharin with particular reference to the urinary bladder.

Male and female Wistar rats were administered sodium saccharin for life (2 yr) either in the drinking water or diet. The maximum palatable dose of saccharin in the drinking water was found to be 2 g/kg/day and, even then, there was some voluntary restriction of fluid intake in the males. By contrast, double this dose--namely 4 g/kg/day, was palatable in the diet. A control group of rats of both sexes received saccharin-free diet and drinking water. Mild urothelial hyperplasias developed from 85 weeks in rats of both sexes receiving saccharin either in the drinking water or diet; the incidence was statistically significant in both the bladders and kidneys of rats receiving the higher dose of saccharin in the diet, but in the kidneys only of rats receiving the lower dose of saccharin in the drinking water. Telangiectasia of the vasa recta was significant in saccharin-treated rats of both sexes at both doses. A very low incidence of bladder tumours, exclusively in males receiving the higher saccharin dose in the diet was seen from 95 weeks. No consistent relationship between bladder epithelial hyperplasias and crystalluria could be demonstrated, although all 3 bladder tumours were associated with some form of mineralisation. Results suggest a particular susceptibility of males to saccharin treatment. The possibility that saccharin may promote, or enhance, the development of latent tumour cells already present in the experimental population, rather than initiate carcinogenesis per se is considered.

Animals↗
PubMed1979

Hormone replacement therapy in the menopause: a suitable animal model.

Female CBA mice, aged 11 months, were treated cyclically with oral ethynyl oestradiol or oestrone sulphate for 3 months. The ovaries of all animals appeared to be atrophied. Target tissues throughout the genital tract showed a response to both oestrogens. Electron microscopy of both the endometrium and the urothelium demonstrated morphological changes characteristic of increased cellular metabolic activity in the treated mice. Endometrial hyperplasia developed in both treatment groups but more pronounced epithelial changes occurred with oestrone sulphate. This hyperplasia was accompanied by a doubling in the number of uterine cytoplasmic oestrogen receptors. A 50% fall in serum levels of luteinizing hormone in the treated mice revealed that the hypothalamic-pituitary system was still intact. Both oestrogens improved skeletal balance by changes in cortical-endosteal bone remodelling. The results suggest that the CBA strain of mouse is a suitable model for the study of the human climacteric and its response to hormone replacement therapy.

Animals↗
PubMed1977

The importance of synergy between weak carcinogens in the induction of bladder cancer in experimental animals and humans.

It is now well established that the interaction of multiple environmental factors may increase the incidence of some human cancers more than exposure to a single carcinogen. With an in vivo experimental rat model, we have demonstrated a synergistic effect in bladder carcinogenesis between a subcarcinogenic dose of the strong bladder carcinogen, N-methyl-N-nitrosourea, and saccharin- or cyclamate-containing diets. If these artificial sweeteners are capable of interacting with other environmental bladder carcinogens, their potential for increasing the incidence of human bladder cancer is greater than many more potent chemical carcinogens, because of their wide distribution as food additives to all sections of the population. Retrospective epidemiology shows no evidence of such risk from saccharin at current levels of consumption. No comparable studies are available for cyclamate, which was consumed in greater quantities but for relatively few years. It is emphasized that it is possible for interaction between multiple factors to contribute to the incidence of human bladder cancer as it does in other human organs and in other animal species.

2-Naphthylamine↗
PubMed1975

Evaluation of a new model to detect bladder carcinogens or co-carcinogens; results obtained with saccharin, cyclamate and cyclophosphamide.

A sensitive rat model has been designed to detect potential weak bladder carcinogens or co-carcinogens. The test compound is given to animals which have received a single initiating, but non-carcinogenic, dose of N-methyl-N-nitrosourea (MNU). The model has been used to investigate two compounds currently under suspicion as weak bladder carcinogens, namely sodium saccharin and sodium cyclamate, and one compound known to be cytotoxic but not carcinogenic for the bladder epithelium namely cyclophosphamide. For comparison, these three compounds were also tested as solitary carcinogens in animals not pre-treated with MNU. At the very high dose levels used, sodium saccharin and sodium cyclamate were weak solitary carcinogens producing 4/253 and 3/228 bladder tumours respectively, and the first of these tumours did not appear for more than 80 weeks. When tested in the MNU/rat model more than half the animals receiving either sodium saccharin or sodium cyclamate developed bladder tumours from 10 weeks onwards. By contrast, cyclophosphamide failed to produce any tumours when tested either as a solitary carcinogen or in the MNU/rat model. It must be emphasized that the doses of saccharin and cyclamate used were far higher than those consumed by man, including diabetics, and these results should not be directly extrapolated to man without careful consideration of many other factors including negative epidemiological findings. The theoretical basis of the model is discussed and also the relevance, in terms of environmental human exposure, of detecting compounds which have a synergistic effect with other known bladder carcinogens. It appears that this model can be used to detect a carcinogenic or co-carcinogenic potential in compounds which are organotropic for the bladder more rapidly and with fewer animals than if the compounds are tested as solitary carcinogens by more conventional methods. It is suggested that it could be used to detect those compounds which require further investigation.

Administration, Oral↗