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PubMed2003

Enhancement of urinary bladder carcinogenesis by combined treatment with benzyl isothiocyanate and N-butyl-N-(4-hydroxybutyl)nitrosamine in rats after initiation.

Previously we reported that benzyl isothiocyanate (BITC) strongly enhanced rat urinary bladder carcinogenesis after initiation with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), while potently inhibiting BBN-induction of lesions when given simultaneously with the carcinogen. In the present experiment, the effects of simultaneous treatment with BITC and low-dose BBN on the post-initiation period of rat urinary bladder carcinogenesis were examined. After treatment with 500 ppm BBN for 4 weeks for initiation, groups of 20, 6-week-old, F344 male rats were given 25 ppm BBN alone, basal diet alone, or 100 or 1000 ppm BITC in the diet together with or without 25 ppm BBN in their drinking water for 36 weeks and then killed for autopsy. Further groups consisting of 10 rats each were similarly given BITC or the basal diet together with or without 25 ppm BBN, without initiation treatment. In the initiated groups receiving subsequent BBN exposure, papillary and nodular hyperplasia, dysplasia and carcinoma incidences were significantly increased, and they were further increased by the combined treatment with 100 and 1000 ppm BITC in a dose-dependent manner. In the non-initiation groups, carcinomas were only observed in a single rat in each of the BBN-treated control and BBN/BITC 100 ppm treatment groups. The results indicate that simultaneous treatment with BITC and a low dose of BBN does not inhibit, but rather enhances rat urinary bladder carcinogenesis after appropriate initiation, and further suggest that BITC may be a human risk factor, at least in high-risk populations.

Animals↗
PubMed2003

Significance of overexpression of metallothionein in mouse urinary bladder focal lesions induced by treatment with N-butyl-N-(4-hydroxybutyl)-nitrosamine.

Metallothionein (MT) is expressed in various types of human tumors, including transitional cell carcinomas of the urinary bladder, but its biological significance remains unclear. In the present study, the role of MT in urinary bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) treatment was investigated using C57BL/6 mice. One hundred 5-week-old male C57BL/6 mice were divided into two groups, which were given drinking water with or without 0.05% BBN throughout the experimental period. Subgroups of ten animals from each group were sacrificed at weeks 5, 10, 15, 20 and 25, and urinary bladder samples were examined immunohistochemically for MT, proliferating cell nuclear antigen (PCNA) and apoptosis. MT was found to be abundant in normal-looking mucosa, but decreased with progression from precancerous lesions to invasive carcinoma in the urinary bladder obtained from BBN-treated mice. Lesions could be divided into MT-positive and negative. There was a tendency for greater MT expression in PCNA-positive lesions, while apoptosis was rather associated with MT-negativity. These data suggest that the overexpression of MT may play a role in mouse urinary bladder carcinogenesis.

Animals↗
PubMed1994

Basement membrane and carcinogenesis: ultrastructural observations in the basement membrane of the bladder epithelium in rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN).

This study investigated the structural alterations in the basement membrane (BM) of the bladder epithelium in rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) using transmission electron microscopy. Following administration of BBN, thickening of the BM of the bladder epithelium was observed and remained almost constant from 4 to 20 weeks, although the pathological changes in the rat bladder epithelium induced by BBN altered over the same period of 20 weeks. The reason for this phenomenon can be explained by the increased interfacial area between the basal epithelial cells and the BM of the rat bladder epithelium due to an increase in the number and size of the microvilli on the basal cell surfaces adjacent to the BM. Our results also showed that the frequency of hemidesmosomes increased progressively during the period of carcinogenesis, especially in the lesions of noninvasive transitional cell carcinoma (TCC) in the rat bladder. It is suggested that the neosynthesis of BM components can be carried out both by benign hyperplastic cells and by noninvasive TCC cells of rat bladder. The alterations in the BM thickness may be affected by the changes in the number and size of the microvilli occurring on the basal cell surfaces adjacent to the BM. Both an increased frequency of hemidesmosomes and the neosynthesis of BM are closely related to cell proliferation during carcinogenesis.

Animals↗
PubMed1998

Apoptosis and carcinogenesis: morphologic observations in the rat bladder treated with N-butyl-N-(4-hydroxybutyl)nitrosamine.

BACKGROUND: We investigated the role of apoptosis in rat bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). METHODS: Apoptosis was detected in BBN-induced rat bladder lesions by routine hematoxylin and eosin (H&E) staining, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL), and transmission electron microscopic examinations. RESULTS: After administration of BBN, various pathologic changes were observed in the rat bladder after intervals of between 4 and 28 weeks. Through a comparative study in serial sections, the incidence of apoptosis, detected by either routine H&E staining or TUNEL staining, displayed marked elevation in BBN-induced rat bladder lesions, as compared to that in the normal epithelium of the rat bladder, particularly in invasive transitional cell carcinoma. Apoptotic cells with different morphologic features were ultrastructurally demonstrated in a series of rat bladder lesions. Significant group differences in the incidence of apoptosis were seen among the BBN-induced lesions and the normal epithelium of the rat bladder, and among the invasive transitional cell carcinomas and other lesions, before the tumor cells were seen to invade the rat bladder. CONCLUSION: Our data suggest that apoptosis may be closely related to carcinogenesis and tumor invasion of the rat bladder induced by BBN, and that the comparative study of serial sections, each stained by H&E and TUNEL, combined with electron microscopic observation, may provide the most reliable informations in semiquantitative assessment of apoptosis.

Animals↗
PubMed2006

Cytokeratin-20 and seminal vesicle secretory protein VI as possible marker proteins in urinary bladder preneoplastic lesions induced by N-butyl-N-(4-hydroxybutyl) nitrosamine.

BACKGROUND: A simple and non-invasive methods for the diagnosis of transitional cell carcinoma of the bladder are needed for the prevention of invasive tumor. A proteomic technology has recently been developed to facilitate protein profiling of biological mixtures. We tried to detect the marker proteins by proteomic approach during the initiation stages on N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced bladder carcinogenesis in rats. METHODS: Ten rats in group A were given 0.05% BBN in drinking water for 12 weeks. Other 10 rats in group B with 10 rats were designated as a control group and were not given BBN. Whole urinary bladders of all rats were excised at 12 weeks from the beginning of the experiment. Conventional proteomics was performed with high resolution 2-dimension gel electrophoresis followed by computational image analysis and protein identification using mass spectrometry. RESULTS: A comparison of urinary bladder hyperplasia tissue with control tissue showed that five proteins; actin gamma2 propeptide, cytokeratin-20 (CK-20), proapolipoprotein, alpha2 actin (alpha-cardiac actin) and heat shock 27 kDa protein-1 were over-expressed in hyperplastic tissues. Three proteins; transcription factor myocardin, seminal vesicle secretory protein VI (SVS-VI) precursor and hypothetical protein RMT-7 were under-expressed in hyperplastic tissues. CONCLUSION: In our animal mode, BBN-induced urinary bladder mucosal hyperplasia resulted in an increase in the expression of five proteins and a decrease in the expression of three proteins. Of these, CK-20 and SVS-VI seem to be of particular interest. However other method such as Western blotting seems to be needed for confirmation of these proteins and more information on human bladder tissue is needed for clinical application.

Animals↗
PubMed1984

Dimethyl nitrosamine-induced proliferative and neoplastic lesions in the mouse liver characterized by histopathology and flow cytometric DNA measurements.

Thirty-one liver tumours induced in NMRI mice by treatment of the newborn animals with the carcinogen demethyl nitrosamine were examined histopathologically and by flow cytometric determination of nuclear DNA content. The tumours were classified as nodules of hyperplasia, adenomas or hepato-cellular carcinomas. Single cell suspensions from each tumour were analyzed by flow cytometry. The lesions consisted of cells with stemlines of low ploidy (2c and 4c) as compared to the high ploidy of the surrounding parenchymal cells (4c, 8c and 16c). The hyperplastic nodules contained stemlines of both diploid and tetraploid DNA content, whereas the adenomas and most of the carcinomas were diploid. The possible occurrence of aneuploid cells in the lesions is discussed.

Adenoma↗
PubMed1986

Evaluation of the nitrosamine hypothesis of gastric carcinogenesis in precancerous conditions.

A 24 hour gastric aspiration study was carried out on nine Polya gastrectomy, eight pernicious anaemia, and nine matched control subjects. Intragastric pH, bacteria, nitrite, and N-nitroso compounds were assessed half hourly whilst ambulant and hourly when in bed. Both total and nitrate reducing bacterial counts were positively related to pH (chi 2 = 279.3; p less than 0.001), as was nitrite concentration (F = 19.1; p less than 0.0001). By contrast, total (F = 40.6; p less than 0.0001) and stable (F = 257.4; p less than 0.0001) N-nitroso compound concentrations were negatively related to pH. Clear differences in these gastric juice factors were not apparent between matched control and either pernicious anaemia, or Polya gastrectomy because the Polya gastrectomy and matched control groups were heterogeneous for gastric acidity. Thus, although eight of eight pernicious anaemia subjects were hypoacidic (defined as intragastric pH greater than 4 for greater than 50% of both daytime and night time periods), only five of nine Polya gastrectomy and two of nine matched control subjects were hypoacidic. When subjects were rearranged into hypoacidic (n = 15) and acidic (n = 11) groups, bacterial counts (p less than 0.01) and nitrite concentrations (p less than 0.01) were higher, whereas N-nitroso compounds tended to be lower (NS) in the hypoacidic group. These data suggest that, although hypoacidity predisposes to bacterial overgrowth and nitrite generation, it does not enhance nitrosation. Instead, this is maximal at low pH, suggesting chemical rather than bacterial nitrosation, contrary to the nitrosamine hypothesis of gastric carcinogenesis.

Aged↗
PubMed1999

Effect of fleroxacin on mouse bladder carcinogenesis with N-butyl-N- (4-hydroxybutyl) nitrosamine.

We recently reported fleroxacin significantly affected cell proliferation in a dose-dependent manner in transitional cell carcinoma cell lines. In this study, we investigated the effect of fleroxacin on mouse bladder carcinogenesis with N-butyl-N-(4-hydroxybutyl) nitrosamine (BHBN). Five-week-old C57BL/6 female mice were divided into three groups. The forced oral administrations of fleroxacin (10 or 50 mg/kg/day) were done for 1 week, then the 0.05% BHBN was given for 8 or 12 weeks. Fleroxacin treatments were continued until sacrifice. The mice were sacrificed at 4 weeks or 8 weeks latent period after BHBN administration, and the histological changes in the bladder were examined. Our study suggested that fleroxacin tended to suppress the development of bladder carcinoma or the malignant changes induced by a shorter period of BHBN administration (8 weeks) in mice. However, in the group of the BHBN administration for 12 weeks, there were no significant effects on the prevention of bladder carcinoma in both of the treatment groups with fleroxacin (10 or 50 mg/kg/day). This study did not make it clear that oral administration of fleroxacin suppressed the development of bladder carcinoma induced by BHBN in mice. However, it is very preliminary data and further experiments need to be done with a much higher dose of the fleroxacin or with other kinds of fluoroquinolone antibiotics.

Animals↗
PubMed1987

Effect of phenacetin and caffeine on N-butyl-N-(4-hydroxybutyl)-nitrosamine-initiated urothelial carcinogenesis in rats.

The present experimental study was undertaken to clarify whether phenacetin and caffeine exert a cocarcinogenic and/or promoting effect on N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-initiated urothelial carcinogenesis. BBN was initially administered to female Wistar rats by gavage in 3 consecutive fractionated doses of 100 mg/kg body weight each at 24-hour intervals. Phenacetin was continuously fed at a daily dose of 500 mg/kg body weight, and caffeine was given in the drinking water at a dose of 110 mg/kg body weight/day throughout the experiment. After an experimental period of 21 months the incidence of BBN-induced tumors in the urinary bladder (number of rats with a bladder tumor) had not increased following additional administration of phenacetin alone (47%) or in combination with caffeine (48%) compared with the control group, the animals of which received exclusively BBN (44%). However, there was a significant enhancement of a multifocal tumor development (number of rats with more than 1 tumor in the bladder), when additionally phenacetin was fed alone (44% of the tumor-bearing animals) or in combination with caffeine (47%) compared with the control rats treated with BBN alone which showed only solitary tumors. Similarly, the incidence of a multicentric tumor development had increased, although not significantly, following administration of phenacetin alone or simultaneously with caffeine for 15 months. Caffeine revealed no complete initiating carcinogenic potential for the resting as well as the regenerating bladder urothelium stimulated to proliferate by either a partial cystectomy or cyclophosphamide. Furthermore, no cocarcinogenic and/or promoting activity of caffeine on BBN-initiated bladder tumor development was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Drug-nitrite interactions in human saliva: effects of food constituents on carcinogenic N-nitrosamine formation.

A simple and rapid high-pressure liquid chromatographic assay for monitoring N-nitrosodimethylamine (NDMA) in human saliva was developed. The method was used to study in vitro the effects of common food constituents on NDMA formation in saliva from the interaction of salivary nitrite with aminopyrine and oxytetracycline. Natural phenolic compounds, caffeic acid, and tannic acid, and synthetic additives, erythorbic acid, sorbic acid, propyl gallate, and butylated hydroxytoluene--all inhibited NDMA formation (20-80%). With ascorbic acid, up to 90% inhibition of NDMA synthesis in saliva was observed. In contrast, chlorogenic acid (a phenolic component of coffee) acted as a catalyst (up to 48% increase) of the nitrosamine formation under identical experimental conditions.

Adult↗
PubMedDate not supplied

Induction of the renal pelvic and ureteral carcinomas by N-butyl-N-(4-hydroxybutyl)nitrosamine in SD/cShi rats with spontaneous hydronephrosis.

We attempted to establish an animal model for renal pelvic and ureteral carcinomas. In Experiment 1, Sprague-Dawley (SD)/cShi and SD/gShi strains of male and female rats and Fischer-344 (F-344)/DuCrj and LEW/Crj strains of male rats, 6 wk old, were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 12 wk and then treated without chemical for 10 wk. Only the SD/cShi strain, which has spontaneous hydronephrosis and hydroureter, showed high incidences of carcinomas in the renal pelvises and ureters, whereas the other strains did not. In Experiment 2, SD/cShi and Crj:CD strains of male and female rats, 6 wk old, were exposed to 0.05% BBN for 20 wk. Both sexes of SD/cShi rats had high incidences of bilateral carcinomas in renal pelvises and/or ureters associated with urinary bladder carcinomas, whereas both sexes of Crj:CD rats had urinary bladder tumors only. These results indicate that the SD/cShi strain may be a suitable animal for the induction of renal pelvic and ureteral carcinomas that appear to depend on urine stagnation secondary to hydronephrosis and hydroureter.

Animals↗
PubMedDate not supplied

Promoting effect of monosodium aspartate, but not glycine, on renal pelvis and urinary bladder carcinogenesis in rat induced by N-butyl-N-(4-hydroxybutyl)nitrosamine.

Although the incidences were relatively low, hyperplasias of the renal pelvis and the urinary bladder have been observed in Fischer-344 (F-344) rats after both sodium aspartate and glycine treatments in long-term 2-yr bioassays. In the present study, the effects of these amino acids on development of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-initiated urinary lesions were investigated in male and female F-344/DuCrj rats. F-344 rats of both sexes, 6 wk old at the commencement, were given 0.05% BBN for 4 wk and then treated with one of the amino acids at a level of 5.0% in the drinking water for the following 36 wk. Proliferative lesions in the renal pelvis often associated with necrosis and mineralization were increased in the group treated with BBN followed by sodium aspartate, but not by glycine, in both sexes. The same group demonstrated higher incidences of urinary bladder tumors with increased urinary pH and sodium concentration and decreased creatinine and uric acid, but not accompanying crystallization. These results showed a clear promoting effect of sodium aspartate for urinary carcinogenesis in rats. The mechanisms of the effect on the renal pelvis and urinary bladder might be different.

Animals↗
PubMedDate not supplied

Comparison of uroplakin expression during urothelial carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine in rats and mice.

The expression of uroplakins, the tissue-specific and differentiation-dependent membrane proteins of the urothelium, was analyzed immunohistochemically in N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-treated rats and mice during bladder carcinogenesis. Male Fischer 344 rats were treated with 0.05% BBN in the drinking water for 10 wk and were euthanatized at week 20 of the experiment. BBN was administered to male B6D2F, mice; it was either provided at a rate of 0.05% in the drinking water (for 26 wk) or 5 mg BBN was administered by intragastric gavage twice weekly for 10 wk, followed by 20 wk without treatment. In rats, BBN-induced, noninvasive, low-grade, papillary, transitional cell carcinoma (TCC) showed decreased uroplakin-staining of cells lining the lumen but showed increased expression in some nonluminal cells. In mice, nonpapillary, high-grade dysplasia, carcinoma in situ, and invasive carcinoma were induced. There was a marked decrease in the number of uroplakin-positive cells lining the lumen and in nonluminal cells. This occurred in normal-appearing urothelium in BBN-treated mice and in dysplasic urothelium, in carcinoma in situ, and in invasive TCC. The percentage of uroplakin-positive nonluminal cells was higher in control mice than in rats, but it was lower in the mouse than in the rat after BBN treatment. Uroplakin expression was disorderly and focal in BBN-treated urothelium in both species. These results indicate that BBN treatment changed the expression of uroplakins during bladder carcinogenesis, with differences in rats and mice being related to degree of tumor differentiation.

Animals↗
PubMed1989

The statistical analysis of a carcinogen mixture experiment. III. Carcinogens with different target systems, aflatoxin B1, N-butyl-N-(4-hydroxybutyl)nitrosamine, lead acetate, and thiouracil.

This paper describes factorial experiments designed to determine whether two carcinogens that lead to cancers in different organ systems act synergistically to produce cancers in Fischer 344 rats. Four carcinogens, aflatoxin B1 (AFLA), N-butyl-n-(4-hydroxybutyl)nitrosamine (NBBN), lead acetate (LA), and thiouracil (THIO) were studied in pairwise combinations. Each of the six possible pairs were studied by means of a 4 X 4 factorial experiment, each agent being fed at zero and at three non-zero doses. Methods of analysis designed explicitly for this study were derived to study interaction. These methods were supplemented by standard statistical methods appropriate for single agent studies. Neither synergism nor antagonism was demonstrated in these combined exposure studies. Findings for male and female animals were consistent.

Aflatoxin B1↗
PubMed2002

Simultaneous treatment with benzyl isothiocyanate, a strong bladder promoter, inhibits rat urinary bladder carcinogenesis by N-butyl-N-(4-hydroxybutyl)nitrosamine.

Effects of benzyl isothiocyanate (BITC) on urinary bladder carcinogenesis were examined in rats simultaneously treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Groups of 20 6-wk-old Fischer 344 male rats were given 10, 100, or 1,000 ppm BITC in the diet or a basal diet with 50 ppm BBN in the drinking water for 40 wk and then killed for autopsy. Additional groups consisting of 10 or 9 rats were similarly given BITC or the basal diet alone without BBN treatment. With BBN treatment, dysplasia, papilloma, and carcinoma incidences and multiplicities were dramatically decreased by simultaneous treatment with BITC in a clear dose-dependent manner. In contrast, epithelial hyperplasia was induced in rats treated with 100 and 1,000 ppm BITC without BBN. These results clearly indicate that although BITC may have weak carcinogenic potency, it is a potent chemopreventive agent against bladder tumor induction by BBN.

Animals↗
PubMed2000

Sequential observation of 2,6-dimethylaniline-induced nasal lesions in a rat two-stage nasal carcinogenesis model after initiation with N-bis(2-hydroxypropyl) nitrosamine.

Male F344 rats received diet containing 3,000 ppm 2,6-dimethylaniline (DMA) after initiation with a single subcutaneous injection of 2,400 mg/kg of N-bis(2-hydroxypropyl)nitrosamine (DHPN), and histological and electron microscopic examinations of the nasal cavity were performed at 4, 13, 26 and 52 weeks to examine sequential changes induced by DMA. Severe atrophy of Bowman's glands and epithelial disarrangement were apparent from week 4, followed by dilatation and/or proliferation of Bowman's glands, degeneration of epithelial cells, and proliferation of undifferentiated epithelial cells from week 13. Focal glandular hyperplasias, dysplastic foci, and adenomas were observed from week 26, and carcinomas at 52 week. These nasal lesions were mostly evident in the olfactory mucosa in the nasal cavity, and their severity and/or incidences, other than atrophy of Bowman's glands, increased with the treatment period. Electron microscopically, carcinoma cells demonstrated desmosomes, dense secretory granules identical to those in normal Bowman's glands, a basement membrane, and microvilli. These results suggest that Bowman's glands are the target of DMA, giving rise to nasal carcinomas after DHPN-initiation.

Adenoma↗
PubMed1999

Expression of vascular endothelial growth factor in N-butyl-N-(4-hydroxybutyl)nitrosamine-induced rat bladder carcinogenesis.

Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are proteins implicated in tumor-associated microvascular angiogenesis. Expressions of VEGF and bFGF in various stages of chemical-induced rat bladder carcinogenesis were immunohistochemically investigated. Thirty-two male 6-week-old Wistar rats were given drinking water containing 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 20 weeks. VEGF and bFGF were not detected in the normal bladder epithelium. In simple hyperplasia, intensive expression of VEGF was observed in a few epithelial cells, and the expression of epithelial VEGF became more pronounced in papillary or nodular (PN) hyperplasia and papilloma. In carcinoma, heterogeneous expression of VEGF was observed in focal tumor cells, intensely expressed in the invading tumor cells. Ultrastructurally, carcinoma cells showed VEGF immunoreactivity in the cytoplasmic matrix and some rough endoplasmic reticulum, and VEGF-positive and -negative carcinoma cells were also clearly defined. High levels of VEGF mRNA were observed in the carcinoma. However, bFGF was not detected in the epithelium throughout the carcinogenesis. Increased microvessel counts appeared at simple hyperplasia and became more pronounced in PN hyperplasia, papilloma, and carcinoma (F-test; P < 0.05). In the carcinoma, the microvessel counts of the VEGF-expressing tumor areas were significantly higher than that of the non-VEGF-expressing tumor areas (U-test; P < 0.05). The present study suggests that upregulation of epithelial VEGF may begin at a quite early stage in BBN-induced rat bladder carcinogenesis, but bFGF may not be involved.

Animals↗
PubMed1994

Inhibiting effects of diethylmaleate or NH4Cl on NaHCO3, but not butylated hydroxyanisole, promotion of urinary bladder carcinogenesis in male F344 rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine.

The modifying potential of diethylmaleate (DEM) and NH4Cl on promotion by butylated hydroxyanisole (BHA) or NaHCO3 of urinary bladder carcinogenesis in rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was investigated. Six week old animals received 0.05% BBN for 4 weeks and then BHA (2%) + DEM (0.15%), BHA + NH4Cl (1%), NaHCO3 (3%) + DEM, NaHCO3 + NH4Cl, BHA, DEM, NH4Cl or no supplement, administered during experimental weeks 5-36. BHA and NaHCO3 clearly amplify the induction of papillary or nodular (PN) hyperplasias and papillomas in rats initiated with BBN. The promoting activity of BHA was not affected by simultaneous administration of DEM or NH4Cl. The enhancing effects of NaHCO3, in contrast, were clearly diminished by concurrent administration of either of these agents. DEM itself did not influence lesion development whereas NH4Cl reduced the incidence of papillomas. In a second experiment, rats exposed to the same protocol were killed at week 8, and assessed for levels of lipid peroxides in the bladder tissue. No remarkable alterations were observed in any group. Thus, the fact that DEM did exert inhibiting effects on tumor promotion by NaHCO3 without decreasing the urinary sodium ion concentration or pH and influence on lipidperoxide levels, suggests essential differences in the mechanisms of action of different types of bladder promoters.

Ammonium Chloride↗