Effect of urinary pH on the progression of urinary bladder tumours.

Systemic alkalosis has been postulated to enhance tumorigenesis, whereas systemic acidosis has been implicated to exert a favourable influence on tumour control and regression. In the present study the urinary pH was influenced by feeding acid-forming or base-forming diets, and the effect of alkaline or acid urine on the early and late progression phase of urinary bladder carcinogenicity was investigated in male Wistar rats. Bladder lesions were initiated by N-butyl-N-(4-hydroxybutyl) nitrosamine (0.

Modulation of pancreatic carcinogenesis by antioxidants.

Previously performed short-term (4-month) studies demonstrated that vitamins C and E, beta-carotene and selenium modulate growth of early putative preneoplastic acinar lesions induced in rat pancreas by azaserine. The present paper summarizes the results of long-term studies performed with azaserine-treated rats maintained on diets high in either beta-carotene, vitamins C and E or selenium. It appeared that rats given a diet high in beta-carotene, vitamin C or selenium, but not vitamin E, developed fewer pancreatic tumours than controls.

Dietary fat and carcinogenesis.

Epidemiologic investigations have suggested a relationship between dietary fat intake and various types of cancer incidences. Furthermore, epidemiologic studies as well as studies with animal models have demonstrated that not only the amount but also the type of fat consumed is important. At present, the mechanism by which dietary fat modulates carcinogenesis has not been elucidated.

Lack of inhibitory effects of beta-carotene, vitamin C, vitamin E and selenium on development of ductular adenocarcinomas in exocrine pancreas of hamsters.

The effects of vitamins E and E, beta-carotene and selenium on development of N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic tumours in hamsters were investigated. Dietary supplementation of vitamin C, alone as well as in combination with beta-carotene resulted in consistently lower numbers of advanced ductular lesions. The differences with the controls, however, did not reach the level of statistical significance.

Overexpression of transforming growth factor-alpha and epidermal growth factor receptor, but not epidermal growth factor, in exocrine pancreatic tumours in hamsters.

Using immunohistochemistry, Northern blotting and a semi-quantitative PCR technique, epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha) and epidermal growth factor receptor (EGFR) expression were studied in the pancreas of N-nitrosobis(2-oxopropyl)-amine (BOP)-treated hamsters. After initiation pancreatic carcinogenesis was modulated by a high fat diet or by injections with the cholecystokinin analogue caerulein. Autopsies were performed 6 and 12 months after the last injection with BOP.

Effects of sandostatin, alone and in combination with surgical castration, on pancreatic carcinogenesis in rats and hamsters.

In a previous short-term study (4 months) we found that Sandostatin, when administered prophylactically, inhibited growth of putative pre-neoplastic ductular lesions induced in hamster pancreas by N-nitrosobis(2-oxopropyl)amine (BOP), but not of acinar lesions induced in rat pancreas by azaserine. The present long-term (12 months) study was carried out to investigate the effects of Sandostatin (3 microgram/day), alone and in combination with orchiectomy, on pancreatic carcinogenesis in azaserine-treated rats and BOP-treated hamsters. In order to mimic therapy in humans, treatment of the animals started 4 months after the last injection with carcinogen, when (pre)neoplastic lesions had already developed.

Effects of aminoglutethimide, alone and in combination with surgical castration, on pancreatic carcinogenesis in rats and hamsters.

The present 12-month study was carried out to investigate the effects of the aromatase inhibitor aminoglutethimide, alone and in combination with orchiectomy, on pancreatic carcinogenesis in azaserine-treated rats and N-nitrosobis(2-oxopropyl)-amine-treated hamsters. Treatment of the animals started 4 months after the last injection with the carcinogen. They were surgically castrated and/or treated with aminoglutethimide.

Transforming growth factor-alpha and epidermal growth factor expression in the exocrine pancreas of azaserine-treated rats: modulation by cholecystokinin or a low fat, high fiber (caloric restricted) diet.

Expression of transforming growth factor-alpha (TGF-alpha) and epidermal growth factor (EGF) was studied in normal pancreatic tissue and in (pre)neoplastic pancreatic lesions of azaserine-treated rats. They were given either a low fat, high fiber (low caloric) diet, to inhibit carcinogenesis, or a low fat diet combined with injections of the cholecystokinin analog caerulein to enhance carcinogenesis. The control groups, maintained on a low fat diet, were injected with azaserine or were not treated at all.

Effects of dietary linoleic acid on pancreatic carcinogenesis in rats and hamsters.

It has been suggested that linoleic acid (LA) is responsible for the promoting effect of dietary polyunsaturated fat on pancreatic carcinogenesis via an accelerated prostaglandin synthesis, caused by metabolism of LA-derived arachidonic acid in (pre)neoplastic tissue. The purpose of the present study was to investigate whether dietary LA is the cause of pancreatic tumor promotion by a high fat diet. Five groups of 30 azaserine-treated rats and 5 groups of 30 N-nitrosobis(2-oxopropyl)amine-treated hamsters were maintained for 6 months (rats) and 12 months (hamsters) on high fat (25 weight %) AIN diets containing 2, 4, 6, 10, or 15 weight % LA.

Effects of cholecystokinin and bombesin on development of azaserine-induced pancreatic tumours in rats: modulation by the cholecystokinin receptor antagonist lorglumide.

Cholecystokinin and bombesin have been shown to promote pancreatic growth and development of azaserine-induced acidophilic atypical acinar cell nodules in rat pancreas after treatment for 16 weeks. Lorglumide, a specific cholecystokinin receptor antagonist, inhibited the stimulating effect of cholecystokinin, but not of bombesin. The present study was carried out to determine effects of cholecystokinin and bombesin, alone and in combination with lorglumide, on pancreatic growth and carcinogenesis after chronic treatment.

Role of cholecystokinin in dietary fat-promoted azaserine-induced pancreatic carcinogenesis in rats.

The role of cholecystokinin in dietary fat-promoted pancreatic carcinogenesis was investigated in azaserine-treated rats, using lorglumide, a highly specific cholecystokinin-receptor antagonist. The animals were killed 8 months after the start of treatment. Cholecystokinin, but not dietary unsaturated fat, increased pancreatic weight.

Effects of orchiectomy, alone or in combination with testosterone, and cyproterone acetate on exocrine pancreatic carcinogenesis in rats and hamsters.

The results of a previous 4-mo study in azaserine-treated rats and BOP-treated hamsters indicated that orchiectomy inhibited pancreatic growth and development of putative preneoplastic lesions in the exocrine pancreas of rats but not hamsters. This 12-mo study was carried out to investigate the effects of orchiectomy, alone and in combination with testosterone, and of treatment with cyproterone acetate on pancreatic carcinogenesis in azaserine-treated rats and BOP-treated hamsters. Treatment started 4 mo after injection of the carcinogen.

Effects of sandostatin and castration on pancreatic carcinogenesis in rats and hamsters.

The effects of treatment with the somatostatin analogue Sandostatin, separately and in combination with surgical castration, on the development of azaserine-induced lesions in rat pancreas and N-nitrosobis(2-oxopropyl)amine (BOP)-induced lesions in hamster pancreas were investigated. The animals were divided in 4 groups and treated as follows: (a) controls, injected s.c.

Effects of the synthetic trypsin inhibitor camostate on the development of N-nitrosobis(2-oxopropyl)amine-induced pancreatic lesions in hamsters.

Trypsin inhibitors have been shown to promote pancreatic growth as well as the development of pancreatic tumours in rats. The present study was carried out to examine the effects of the synthetic trypsin inhibitor camostate on the growth of the pancreas and on the development of pancreatic preneoplastic and neoplastic lesions in hamsters treated with N-nitrosobis(2-oxopropyl)amine. A specific cholecystokinin-receptor antagonist was administered to determine the role of cholecystokinin in camostate action.

Effects of castration, alone and in combination with aminoglutethimide, on growth of (pre)neoplastic lesions in exocrine pancreas of rats and hamsters.

We studied the effects of hormonal manipulation by orchiectomy, alone or in combination with the aromatase inhibitor aminoglutethimide (AGT), and by luteinizing hormone-releasing hormone agonist (LH-RH-A) (goserelin) treatment on the development of early putative (pre)neoplastic lesions induced in the pancreas of rats and hamsters by azaserine and N-nitrosobis(2-oxopropyl)amine respectively. Treatment of the animals started 1 week after the last injection with carcinogen and continued for 4 months. Orchiectomy caused a significant inhibition of growth of acidophilic atypical acinar cell nodules in the rat model, whereas surgical castration did not show an effect in the hamster model.

Effects of bombesin on the development of N-nitrosobis(2-oxopropyl)amine-induced pancreatic lesions in hamsters.

Bombesin (BBS) has been shown to promote pancreatic growth as well as the development of pancreatic (pre)neoplasia in rats. The present study was carried out to determine the effects of bombesin on pancreatic growth and on the development of pancreatic (pre)neoplastic lesions in hamsters treated with N-nitrosobis(2-oxopropyl)amine (BOP). Bombesin caused an increase in growth of the pancreas accompanied by a decrease in the number of (pre)neoplastic ductular pancreatic lesions.

Early indicators of exocrine pancreas carcinogenesis produced by non-genotoxic agents.

In the past 40 years the incidence of pancreatic cancer in many Western countries had increased. Since no single factor responsible for the development of pancreatic cancer has been identified, it is believed that non-genotoxic factors may play an important role in the pathogenesis of this highly fatal form of cancer. Focal abnormalities of acinar cells, referred to as atypical acinar cell foci or nodules, occur spontaneously in rats and some other species.

Magnetic resonance imaging compared with hormonal effects and histopathology of estrogen-induced pituitary lesions in the rat.

Estrogen-induced pituitary lesions in rats were studied in time-sequence experiments using magnetic resonance imaging (MRI), hormone determinations and light microscopy. The main purpose of the study was to evaluate the usefulness of MRI in comparison with conventional biochemical and histopathological methods for detecting the pituitary lesions as early as possible and to follow their development. Measurements were made at 15 time points, ranging from 1 h to 272 days after s.

Role of cholecystokinin in the development of BOP-induced pancreatic lesions in hamsters.

Cholecystokinin (CCK) has been shown to promote pancreatic growth and azaserine-induced pancreatic carcinogenesis in rats. The present study was carried out to determine effects of CCK on pancreatic growth and carcinogenesis in the N-nitrosobis(2-oxopropyl)amine (BOP) hamster model. One hundred male Syrian golden hamsters were injected s.

Upper respiratory tract tumors in Cpb:WU (Wistar random) rats.

A survey is given of upper respiratory tract tumors in Cpb:WU (Wistar random) rats. Data were collected from ten 24- to 30-month toxicity/carcinogenicity studies and from one 12-month study. Nasal tumors may lead to dyspnea, mouth breathing, and nasal discharge.

Modulation of putative preneoplastic foci in exocrine pancreas of rats and hamsters. Interaction of dietary fat and coffee.

The effects of coffee and dietary fat (alone and in combination) on the development of preneoplastic lesions in exocrine pancreas were investigated in rats and hamsters, treated with azaserine or N-nitrosobis(2-oxopropyl)amine, respectively. The animals were given the respective diets (5% or 25% corn oil) and coffee (instead of drinking water) within one week after the treatment with carcinogen. At four months postinitiation, the pancreata were quantitatively examined for the number and size of preneoplastic foci.

Modulation of dietary fat-promoted pancreatic carcinogenesis in rats and hamsters by chronic ethanol ingestion.

The effect of chronic ethanol ingestion on dietary fat-promoted pancreatic carcinogenesis was investigated in rats and hamsters. Rats were given a single i.p.

Nasal tumours in rats after severe injury to the nasal mucosa and prolonged exposure to 10 ppm formaldehyde.

To study the significance of damage to the nasal mucosa for the induction of nasal tumours by formaldehyde in rats, a long-term inhalation study was conducted in which male rats with severely damaged or undamaged nose were exposed 6 h/day for 5 days/week to 0, 0.1, 1.0 or 10 ppm formaldehyde vapour for 28 months, or for 3 months followed by a 25-month observation period.

Modulation of dietary fat-promoted pancreatic carcinogenesis in rats and hamsters by chronic coffee ingestion.

The effect of chronic coffee ingestion on dietary fat-promoted pancreatic carcinogenesis was investigated in rats and hamsters. Rats were given a single i.p.

Inhibition of dietary fat promoted development of (pre)neoplastic lesions in exocrine pancreas of rats and hamsters by supplemental selenium and beta-carotene.

The modulating effects of selenium and beta-carotene on the development of putative preneoplastic foci in exocrine pancreas were investigated in rats and hamsters, treated with azaserine and N-nitrosobis(2-oxopropyl)amine (BOP), respectively. The animals were fed a semipurified diet high in saturated fat (20% lard) either supplemented or not with beta-carotene or selenium. A separate group maintained on a diet low in saturated fat (5% lard) was incorporated as an extra control group.