RESUMEN
Albino noninbred weanling male and female rats were fed a basic grain diet (Group 1), a basic diet supplemented with 0.5% nicotinamide (Group 2), a basic diet containing 33% bracken fern (BF) (Group 3), or a basic diet supplemented with 33% BF and 0.5% nicotinamide (Group 4) for 58 weeks. Dietary nicotinamide decreased the BF-induced incidence of both intestinal and bladder tumorigenesis by about 40%. The inhibitory effect of nicotinamide on the BF-induced intestinal and bladder tumors was significant at p less than 0.05 and p less than 0.01, respectively.
Asunto(s)
Neoplasias Intestinales/prevención & control , Niacinamida/uso terapéutico , Plantas Tóxicas , Neoplasias de la Vejiga Urinaria/prevención & control , Animales , Peso Corporal/efectos de los fármacos , Femenino , Neoplasias Intestinales/etiología , Masculino , NAD/metabolismo , Neoplasias Experimentales/etiología , Neoplasias Experimentales/prevención & control , Ratas , Ratas Endogámicas , Neoplasias de la Vejiga Urinaria/etiologíaRESUMEN
Albino noninbred weanling male and female rats were fed a basic grain diet (Group 1) or a basic diet supplemented with 33% bracken fern [BF (Group 2)] or 0.1% quercetin [purity, > 99% (Group 3)] for 58 weeks. The quantities of quercetin and kaempferol (a close structural analog) in BF as glycosides were determined to be 0.57 and 1.1 g, respectively, per kg of dried BF. Estimated mean total cumulative doses (mmol) per rat were: Group 1, quercetin, males and females < 0.03; kaempferol, males and females < 0.03; Group 2, quercetin, males 5.8, females 5.2; kaempferol, males 11.9, females 10.8; and Group 3, quercetin, males 27.8, females 25.3; kaempferol, males and females < 0.03. Growth of rats fed BF or quercetin was comparable but significantly (p < 0.01) slower after 24 weeks than that of Group 1. Mean survivals (weeks) of rats of all groups were: Group 1, 58 +/- 7 (S.D.); Group 2, 51 +/- 13; and Group 3, 56 +/- 8. They were not significantly different, although rats fed BF tended to die earlier secondary to intestinal tumor-induced intussusception and obstruction. The following incidences of intestinal or bladder neoplasms in male or female rats, respectively, were observed: Group 1, intestinal and bladder, males, 0 of 9, females, 0 of 10; Group 2, intestinal, males, 7 of 8, females, 10 of 11; bladder, males, 6 of 8, females 8 of 11; Group 3, intestinal, males, 6 of 7, females, 14 of 18; bladder, males, 2 of 7, females, 3 of 18. The histopathology of neoplasms of the 2 target organs was identical for rats of Groups 2 and 3. Multiple ileal intestinal neoplasms of rats fed quercetin included: adenoma, 4; fibroadenoma, 7; and adenocarcinoma, 9 (with mesenteric metastases, 3). The 5 bladder tumors were papillary or sessile transitional cell carcinomas.
Asunto(s)
Flavonoides/toxicidad , Neoplasias Intestinales/inducido químicamente , Plantas Tóxicas , Quercetina/toxicidad , Neoplasias de la Vejiga Urinaria/inducido químicamente , Adenocarcinoma/inducido químicamente , Adenocarcinoma/patología , Adenofibroma/inducido químicamente , Adenoma/inducido químicamente , Adenoma/patología , Animales , Peso Corporal , Carcinoma de Células Transicionales/inducido químicamente , Carcinoma de Células Transicionales/patología , Dieta , Femenino , Neoplasias Intestinales/patología , Masculino , Plantas Tóxicas/análisis , Quercetina/análisis , Ratas , Factores de Tiempo , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
F344 inbred and Sprague-Dawley noninbred rats were fed a basic diet (groups 1 and 7) or a basic diet supplemented with 0.1% (later, 0.2 and 0.4%) tannin (group 2) isolated from bracken fern (Pteridium aquilinum) (BF), 33% BF (groups 3 and 6), 2% chloroform fraction of BF (group 4), or 4% tannin-free fraction of BF (group 5). The following incidences of intestinal or bladder tumors were observed: group 1, intestinal and bladder, 0/16; group 2, 0/21; group 7, 0/16; groups 4 and 5, intestinal, 7/15, bladder, 0/15; group 3, intestinal, 19/20, bladder, 12/20; and group 6, intestinal, 22/30, bladder, 15/30. The chloroform-methanol fraction prepared from urine of rats fed BF, chloroform fraction of BF, or tannin-free fraction of BF demonstrated mutagenicity for Salmonella typhimurium TA 100 but not for TA 98. No mutagenicity was detected in other prepared fractions. F344 rats in group 8 received weekly sc injections of tannin solution (0.1 g/kg body wt) for 38 weeks, and 16/20 developed palpable tumors that were malignant fibrous histiocytomas at the injection site. No tumor was present in any rat of control group 9.
Asunto(s)
Neoplasias Intestinales/inducido químicamente , Plantas Comestibles , Taninos/toxicidad , Neoplasias de la Vejiga Urinaria/inducido químicamente , Animales , Carcinógenos , Femenino , Inyecciones Subcutáneas , Masculino , Mutágenos , Plantas Tóxicas , Quercetina/toxicidad , Ratas , Salmonella typhimurium/efectos de los fármacos , Taninos/administración & dosificación , Taninos/orinaAsunto(s)
Carcinógenos , Leche/toxicidad , Mutágenos , Neoplasias Experimentales/inducido químicamente , Plantas Comestibles , Animales , Bovinos , Femenino , Humanos , Neoplasias Intestinales/inducido químicamente , Neoplasias Renales/inducido químicamente , Masculino , Ratones , Ratas , Salmonella typhimurium/efectos de los fármacos , Neoplasias de la Vejiga Urinaria/inducido químicamenteRESUMEN
The inhibitory effect of butylated hydroxyanosole (BHA), disulfiram, calcium chloride, and polyvinylpyrrolidone (PVP) on the intestinal and urothelial carcinogenicity of bracken fern (BF) was determined in albino rats. Of 10 groups of rats, one group received a normal diet, one received a BF-containing diet (one-third of diet by weight), four received a normal diet with one of the following supplements, and four received BF-containing diet with one of the following: BHA (5 mg/g diet); disulfiram (5 mg/g diet); PVP (50 mg/g diet); or calcium chloride (20 mg/g diet). At 12 months of the experiment, the following results were noted: in the BF-treated group, 30 rats (100%) exhibited intestinal tumors and 22 of 30 (73%) urinary bladder tumors. In the BF-BHA group, 15 of 20 rats (75%) showed intestinal tumors and 12 of 20 rats (60%) urinary bladder tumors. Of the 16 rats in the BF-disulfiram group, 12 (80%) had intestinal and 10 (62.5%) had urinary bladder tumors. In the BF-calcium chloride group, intestinal tumors arose in 16 of 23 rats (70%) and urinary bladder tumors in 4 of 23 rats (17%), while in the 28 BF-PVP rats, 26 (93%) exhibited tumors of the intestine and 5 (18%) tumors of the urinary bladder. Dietary BHA, disulfiram and calcium chloride decreased the incidence of intestinal tumors by about 25--30% (p less than 0.01). Similarly, PVP and calcium chloride inhibited BF-induced urinary bladder carcinogenesis by about 80% (p less than 0.001). No tumors were detected in groups receiving either normal diet or normal diet supplemented with BHA, disulfiram, calcium chloride or PVP.
Asunto(s)
Anisoles/farmacología , Hidroxianisol Butilado/farmacología , Cloruro de Calcio/farmacología , Carcinógenos Ambientales/antagonistas & inhibidores , Disulfiram/farmacología , Plantas Comestibles , Povidona/farmacología , Animales , Dieta , Neoplasias/inducido químicamente , RatasRESUMEN
Germfree and conventional Sprague-Dawley rats were assessed for their susceptibility to intrarectally injected N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or N-methyl-N-nitrosourea (MNU). Adenocarcinoma of the colon was induced in germfree and conventional rats by both MNNG and MNU. The colons of germfree rats were more susceptible to the direct-acting carcinogens, as manifested by earlier morbidity and development of colon tumors (50% tumors within 30-35 wk), than were those of conventional rats (50% colon tumors within 48-50 wk). Germfree and conventional male rats were more susceptible to the carconogens than were their female germfree and conventional counterparts. Young (30 days old at the start of the experiment) germfree rats developed colon tumors more quickly (15-20 wk) than did older (60 days) germfree rats after intrarectal injections of MNNG. No colon tumors were observed in germfree and conventional rats after 75 weekly intrarectal injections with a buffer. Transplantation of an adenocarcinoma induced with MNU in a female rat to germfree and conventional rats showed that it was easily transplantable, required no immunosuppression, and had essentially the same morphologic characteristics as did the primary tumor.
Asunto(s)
Adenocarcinoma/etiología , Factores de Edad , Neoplasias del Colon/etiología , Intestinos/microbiología , Factores Sexuales , Adenocarcinoma/inducido químicamente , Adenocarcinoma/patología , Animales , Neoplasias del Colon/inducido químicamente , Neoplasias del Colon/patología , Esquema de Medicación , Femenino , Vida Libre de Gérmenes , Masculino , Metilnitronitrosoguanidina/administración & dosificación , Metilnitrosourea/administración & dosificación , Trasplante de Neoplasias , Neoplasias Experimentales/inducido químicamente , Neoplasias Experimentales/etiología , Neoplasias Experimentales/patología , Ratas , Factores de Tiempo , Trasplante HomólogoRESUMEN
Histologic examination of the urinary bladders of albino rats fed bracken fern (Pteris aqulinum) showed epithelial hyperplasia in all test animals after 3 weeks of feeding and nuclear abnormalities at 4 to 6 weeks. Epithelial tumors were present in animals surviving more than 12 weeks, and invasion of subepithelial tissue occurred in animals sacrificed after this time. Carcinoma in situ, comparable to that in man, was not observed before invasive carcinoma, but was noted later in the surface epithelium adjacent to invasive carcinoma. Transitional cell carcinomas originated from hyperplastic epithelium, squamous cell carcinomas from metaplastic squamous epithelium, and papillary carcinomas from papillomas. Papillomas were preceded by epithelial hyperplasia. The results suggest that hyperplasia precedes bladder carcinoma in rats fed bracken fern.
Asunto(s)
Carcinógenos , Plantas Comestibles , Neoplasias de la Vejiga Urinaria/inducido químicamente , Animales , Carcinoma Papilar/inducido químicamente , Carcinoma Papilar/patología , Carcinoma de Células Escamosas/inducido químicamente , Carcinoma de Células Escamosas/patología , Carcinoma de Células Transicionales/inducido químicamente , Carcinoma de Células Transicionales/patología , Femenino , Hiperplasia/patología , Masculino , Papiloma/inducido químicamente , Papiloma/patología , Ratas , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
The effects of allopurinol on the induction of bladder cancer by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT), excretion of urinary tryptophan metabolites, hepatic nitroreductase activity, and the acid-soluble thiol content of liver and blood in weanling female Fischer rats were investigated. Four groups of rats were given normal diet or normal diet supplemented with 0.005% allopurinol, 0.188% FANFT, or 0.005% allopurinol-0.188% FANFT. Transitional cell carcinomas appeared in 3 of 30 rats (10%) at 15 weeks and in 7 of 44 rats (16%) at 20 weeks in the FANFT-treated group; the carcinomas appeared in 14 of 35 rats (40%) at 15 weeks and in 27 of 50 rats (54%) at 20 weeks in the FANFT-allopurinol-treated group. Growth rate was not affected by allopurinol and FANFT. Allopurinol alone caused no morphological change in the epithelial cells of the urinary bladder but decreased hepatic cytosol nitroreductase activity. FANFT alone had no effect on hepatic cytosol or microsomal nitroreductase activity but increased hepatic and blood acid-soluble thiol content. FANFT increased the urinary excretion of anthranilic acid glucuronide, kynurenine, acetylkynurenine, and 3-hydroxykynurenine and decreased indican and o-aminohippurate excretion. Allopurinol did not alter the effects of FANFT on the acid-soluble thiol content of liver and blood or the excretion of urinary tryptophan metabolites.
Asunto(s)
Alopurinol/farmacología , Carcinoma de Células Transicionales/inducido químicamente , FANFT/toxicidad , Tiazoles/toxicidad , Neoplasias de la Vejiga Urinaria/inducido químicamente , Animales , Carcinoma de Células Transicionales/metabolismo , Carcinoma de Células Transicionales/patología , Citosol/enzimología , Sinergismo Farmacológico , Femenino , Hígado/metabolismo , Neoplasias Experimentales/inducido químicamente , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Nitrato Reductasas/metabolismo , Ratas , Compuestos de Sulfhidrilo/sangre , Compuestos de Sulfhidrilo/metabolismo , Factores de Tiempo , Triptófano/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
Clinical and morphological characteristics of 139 naturally occurring and 20 braken-fern-induced urinary bladder tumors of cows were studied. Hematuria was prominent and occurred as early as 60 days after braken fern feeding began. Anemia and changes in leukocytes were late manifestations. Papillomas appeared as early as 1 year, whereas invasive carcinomas did not develop until 2.6 years after initiation of feeding. Twenty of 30 cows fed braken fern developed bladder tumors within 5.3 years. None of eight untreated control cows that lived 4 years or six that lived 10 years developed neoplasms. Naturally occurring and fern-induced bladder tumors were epithelial (35%) or mixed epithelial and stromal (55%). Papillomas occurred in 24% and carcinomas in 61% of naturally occurring cases, whereas there were papillomas (40%) and carcinomas (50%) in fern-fed cows. Naturally occurring tumors were metastatic to regional lymph nodes and lung. No metastases were detected in fern-fed cows.
Asunto(s)
Búfalos , Enfermedades de los Bovinos , Intoxicación por Plantas/veterinaria , Neoplasias de la Vejiga Urinaria/veterinaria , Adenoma/patología , Adenoma/veterinaria , Animales , Carcinoma Papilar/patología , Carcinoma Papilar/veterinaria , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/veterinaria , Bovinos , Enfermedades de los Bovinos/patología , Femenino , Hematuria/veterinaria , Recuento de Leucocitos , Metástasis de la Neoplasia , Intoxicación por Plantas/patología , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
We attempted to isolate a carcinogenic substance from bracken fern (Pteridium aquilinum), a naturally occurring toxicant responsible for the production of chronic enzootic hematuria and urinary bladder cancer of cattle and carcinogenic for various target organs of several species. Hot methanol extracts of bracken fern were solubilized in water and extracted with chloroform followed by a mixture of n-butanol-butanone (1:1). That fraction was dried and triturated with ether-methanol (4:1), n-butanol, and finally absolute ethanol. The insoluble residue was dissolved in 10% aqueous methanol and passed through Dowex 1 OH-, Dowex 50 H+, or Dowex 1 OH- and then Dowex 50 H+ ion exchange resins. A condensed tannin, isolated from one ot the fractions, was identical to that isolated from bracken fern by the caffeine procedure used for the separation of tannins from other plant constituents. Three systems were used for bioassay; induction of bladder carcinoma by implantation of cholesterol pellets containing bracken fern fractions into the bladder lumens of mice; acute toxicity by ip injection of brachen fern fraction into mice; and growth inhibition of Escherichia coli. The following fractions induced significantly greater incidences of bladder carcinoma than did cholesterol pellets only: tannin, Dowex 50 H+, residue, n-butanol, and methanol. Tiliroside, a component of bracken fern fractions into the bladder lumens of mice; acute genic acid, and quercetin were not carcinogenic. Tannin was the most toxic (mean lethal dose: 0.16 mg/g) and carcinogenic. None of the carcinogenic fractions inhibited growth of E. coli.
Asunto(s)
Plantas/análisis , Taninos/aislamiento & purificación , Neoplasias de la Vejiga Urinaria/inducido químicamente , Escherichia coli/efectos de los fármacos , Dosificación Letal Mediana , Metanol , Neoplasias Experimentales/inducido químicamente , Taninos/toxicidadRESUMEN
Tumours of the urinary bladder are uncommon in all domestic animals except cattle in certain regions. Where cattle eat bracken (Pteridium aquilinum) there is a high incidence of these tumours. Epithelial tumours are the most frequently encountered neoplasms in cattle and in dogs-the two species most studied. They are described under the following names: papilloma, adenoma, transitional cell carcinoma (with variants), squamous cell carcinoma, adenocarcinoma, and undifferentiated carcinoma.