Immunotoxic effects of prolonged dietary exposure of male rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

The effects of low level exposure of rats to 2,3,7,8-tetrachlorodibenzo-p- dioxin (TCDD) on their immune system was investigated Dietary administration to young adult male Leeds strain rats of a total dose of 3 micrograms/kg body weight of TCDD resulted in an exposure duration-dependent reduction of in vitro lipopolysaccharide-induced production of interleukin (IL)-1 in cultures of their splenic macrophages. A 30-day exposure produced approximately 30% suppression and 180-day exposure produced approximately 52% suppression. This reduction did not negatively influence lipopolysaccharide- induced proliferation of B cells, instead an enhancement of B cell proliferation was observed after 30 days exposure.

Immunotoxic effects of exposure of rats to xenobiotics via maternal lactation. Part I 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Exposure of lactating female Leeds rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) resulted in a reduction in the body, spleen and liver weights of their male offspring at 130 days of age. None of the total administered doses (0.2, 1.

Inhibitory effect of a cholecystokinin antagonist on pancreatic carcinogenesis after pancreatobiliary diversion.

The role of cholecystokinin (CCK) has been explored in pancreatic carcinogenesis following pancreatobiliary diversion (PBD), using the specific CCK receptor antagonist CR-1409. Male Wistar rats (n = 80) weighing 70-100 g were given weekly i.p.

Duodenogastric reflux enhances growth and carcinogenesis in the rat pancreas.

Surgery for peptic ulcer disease may increase the risk of pancreatic cancer. The effect of duodenogastric reflux on pancreatic carcinogenesis was tested, and changes in the circulating levels of cholecystokinin (CCK) and gastrin were measured. Male Wistar rats (n = 40) weighing 250-300 g were randomized to undergo gastrotomy (control) or split gastrojejunostomy (to produce complete duodenogastric reflux) and then to receive azaserine (30 mg/kg/week intraperitoneally) or saline injections for 3 weeks.

Bile acids do not modify the effects of pepsin on the fine structure of human oesophageal epithelium.

Oesophageal mucosal specimens (n = 250) were taken from 25 normal subjects (14 females, 11 males; median age 52 years; range 19-63 years) and incubated in physiological saline, pepsin and bile acid solutions to determine whether conjugated bile acids modify the epithelial cytotoxic action of pepsin. Short (5 min) and long (22 min) incubations were carried out and the results were assessed by transmission electron microscopy. Six different parameters of epithelial damage were scored (0-4) by a single 'blinded' pathologist for each of four epithelial layers.

Enhancing effect of partial gastrectomy on pancreatic carcinogenesis.

The controversial issue of enhanced pancreatic carcinogenesis following partial gastrectomy has been explored in male Wistar rats (n = 40) weighing 250-300 g. Animals were randomised to receive either 60% distal gastrectomy with Roux-en-Y reconstruction or gastrotomy and resuture (control). Immediately after operation each group was further divided into two subgroups, receiving i.

Effects of dietary fatty acids on the early stages of neoplastic induction in the rat pancreas. Changes in fatty acid composition and development of atypical acinar cell nodules.

Diets enriched with fat, especially unsaturated fat, promote experimental pancreatic carcinogenesis, but little is known of the effects of individual fatty acids. The effect of stearic and oleic acid on pancreatic fatty acids and atypical acinar cell nodules (preneoplastic lesions) was studied in 14-day-old weanling male Leeds strain rats (n = 60) given the carcinogen azaserine. Rats were allocated to one of six groups: untreated controls (n = 10), 20% stearic acid diet (n = 10), 20% oleic acid diet (n = 10), carcinogen alone (n = 10), carcinogen plus 20% stearic acid diet (n = 10) or carcinogen plus 20% oleic acid diet (n = 10).

Pancreatobiliary diversion enhances experimental pancreatic carcinogenesis.

Since compensatory hyperplasia promotes experimental carcinogenesis in the gut, we tested the ability of two surgical models of pancreatic growth to promote pancreatic carcinogenesis. Male Wistar rats (n = 60) weighing 250-300 g underwent pancreatobiliary diversion (PBD), 90% small bowel resection (PSBR) or triple transection and reanastomosis of the small intestine (controls). Postoperatively, each group received azaserine (20 mg kg-1 wk-1 i.

Quantitative electron microscopy of carcinogen-induced alterations in hepatocyte rough endoplasmic reticulum. II. Modulation of the effects of 3'MeDAB by adrenalectomy and adrenal corticosteroids.

A quantitative electron microscope study was made of the effects of bilateral adrenalectomy (ADX) and deoxycorticosterone acetate (DOCA) on the state of aggregation of hepatocyte rough ER cisternae in both untreated and 3'MeDAB-fed Leeds strain rats. Disaggregation of hepatocellular rough ER appears to be a common response of the rat liver to hepatocarcinogenic insult, while ADX and DOCA treatment are known to inhibit the chemical induction of neoplasia in this species. In untreated animals both ADX and DOCA significantly increased the mean number of cisternae per array or stack, while an even more pronounced effect was obtained from a combination of the two.

Effect of fasting on aggregation of hepatocyte rough endoplasmic reticulum in adrenalectomized and 3'MeDAB-treated rats: quantitative electron microscope study.

A method for the quantitative analysis of the degree to which hepatocyte rough endoplasmic reticulum (ER) is arranged into parallel arrays was used to study the effect of fasting on rough ER aggregation in rat liver cells following either bilateral adrenalectomy or administration of the carcinogenic azo dye 3'-methyl-4-dimethylaminoazobenzene (3'MeDAB). One group of male inbred Leeds strain rats was subjected to bilateral adrenalectomy (ADX): after 1 week half of the animals were fasted for 24 h whereupon the whole group was killed. A second group of rats, fed for 4 weeks on a diet containing 0.

Quantitative electron microscopy of carcinogen-induced alterations in hepatocyte rough endoplasmic reticulum. I. Chronic effect of 3'MeDAB and short-term effects of azo dyes of different carcinogenic potentials.

A new method has been developed for the quantitative analysis of an ultrastructural change in hepatocyte rough endoplasmic reticulum (ER) that is induced by liver carcinogens. Hitherto only subjective observations of this alteration had been made. Male inbred Leeds rats were fed a diet containing 0.

Fine structural alterations induced in the rat hepatocyte by adrenalectomy: influence of deoxycorticosterone acetate or fasting.

Electron microscopy was used to investigate the changes induced by bilateral adrenalectomy (ADX) in rat hepatocytes. Animals were killed at 1 week post-ADX, either with or without a prior 24 h fast. Further studies were carried out at 4 to 5 weeks after ADX to investigate the effect of administering deoxycorticosterone acetate (DOCA) for 4 weeks on the ADX-induced alterations.

Induction by paracetamol of bladder and liver tumours in the rat. Effects on hepatocyte fine structure.

Groups of male and female inbred Leeds strain rats were fed diets containing either 0.5% or 1.0% paracetamol by weight for up to 18 months.

Histogenesis of pancreatic carcinogenesis in the hamster: ultrastructural evidence.

Pancreatic carcinogenesis in the Syrian hamster, induced by beta-oxidized derivatives of N-nitroso-di-n-propylamine, constitutes a valuable model of human cancer of the exocrine pancreas. In both species the majority of tumors are adenocarcinomas: superficially, on the basis of their histological appearance, these appear to be ductal in origin. However, sequential analysis, by electron microscopy, of the development of pancreatic neoplasia in the hamster model indicates that acinar cells may participate in the histogenesis of "ductal" adenomas and carcinomas.

An electron microscope study of hepatocellular changes in the rat during chronic treatment with acetamide. Parenchyma, foci and neoplasms.

Male Leeds strain rats were fed a diet containing 5.0% by weight of acetamide (AA), for up to 35 weeks, inducing a high incidence of hepatic cell neoplasms. The sequential morphological changes induced by AA in the hepatic parenchymal cells were studied by electron microscopy and were compared with those observed in foci of cellular alteration, neoplastic nodules and hepatocellular carcinomata.

Effects of inhibiting hepatocarcinogenesis upon the early fine structural changes induced in rat hepatocytes by 3'-methyl-4-dimethylaminoazobenzene.

Young adult male Leeds strain rats were fed for up to 10 weeks on diets containing either 0.06% 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB) or 0.06% 3'-MeDAB together with 0.

Induction of liver cell tumours in IF mice by paracetamol.

Groups of male and female IF strain mice were fed a diet containing either 0.5% or 1.0% paracetamol for up to 18 months.

Ultrastructural analysis of pancreatic carcinogenesis. VI. Early changes in hamster acinar cells induced by N-nitroso-bis(2-hydroxypropyl)amine.

Male Syrian golden hamsters were given weekly s.c. injections of 250 mg/kg body weight of N-nitroso-bis(2-hydroxypropyl)amine (BHP) for up to 15 weeks.

Ultrastructural analysis of pancreatic carcinogenesis. V. Changes in differentiation of acinar cells during chronic treatment with N-nitrosobis(2-hydroxypropyl)amine.

An electron microscope study was carried out on changes in the pancreatic acinar tissues of male Syrian hamsters during the course of induction of pancreatic neoplasia by lifetime weekly injections of N-nitroso-bis(2-hydroxypropyl)amine (BHP). The dominant process observed was a loss of differentiation of the acinar cells, leading to the development of a new population of cells that closely resemble centro-acinar or ductular cells. During this process, the original centro-acinar and ductular cells appear to be relatively unaffected by exposure to BHP.

Effects of prolonged oral treatment with N-fluoren-4-ylacetohydroxamic acid on rat liver fine structure.

Inbred male Leeds strain rats were given a diet containing 0.05% N-fluoren-4-ylacetohydroxamic acid for up to 7 months. A modified method for the synthesis of this compound is described.

3-Methylcholanthrene-inhibition of hepatocarcinogenesis in the rat due to 3'-methyl-4-dimethylaminoazobenzene or 2-acetylamino-fluorene: a comparative study.

Male Leeds strain rats were given a diet containing either 0.06% 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB) or 0.05% 2-acetylaminofluorene (2-AAF), alone or together with 0.

Ultrastructural analysis of pancreatic carcinogenesis. IV. Pseudoductular transformation of acini in the hamster pancreas during N-nitroso-bis(2-hydroxypropyl)amine carcinogenesis.

Electron and high resolution light microscope studies were made of the pseudoductular structures that develop in the pancreas of the Syrian hamster during chronic treatment with the pancreatocarcinogen, N-nitroso-bis(2-hydroxypropyl)amine (BHP). These pseudoductules, which precede the development of tumours, arise from acini, whose cells undergo dedifferentiation by selective autophagy of their zymogen granules and granular endoplasmic reticulum. It is proposed that the pseudoductules develop into the ultrastructurally similar cystic foci that appear to be the immediate precursors of pancreatic tumours in this experimental model.

A comparative electron microscope study of early changes in rat liver induced by N-nitrosopiperidine and 2,2',6,6'-tetramethyl-N-nitrosopiperidine.

Inbred male Leeds rats were administered either the liver carcinogen N-nitrosopiperidine or the non-carcinogen 2,2',6,6'-tetramethyl-N-nitrosopiperidine in their drinking water at a concentration of 0.02%. Treatment was continued until the animals were killed, at 12 or 28 days, when their hepatic tissues were removed and examined by electron microscopy.

Ultrastructural analysis of pancreatic carcinogenesis. III. Multifocal cystic lesions induced by N-nitroso-bis(2-hydroxypropyl)amine in the hamster exocrine pancreas.

Hamsters were given weekly injections of the pancreatic carcinogen N-nitroso-bis(2-hydroxypyropyl)-amine for up to 44 weeks. The cystic foci induced by this treatment, which are putative precursor lesions, were studied by high resolution light microscopy and electron microscopy. They were found to consist mainly of cells that closely resembled those of hamster pancreatic adenomas and adenocarcinomas, confirming their status as precursors of these tumors.