Effects of selenium supplementation on hepatocarcinogenesis in rats

Four groups of weanling male Wistar rats (Groups A—D) received diethylnitrosamine (DEN, 40 ppm) in their drinking water for four weeks; after a recovery period of two weeks, they received (for the rest of the experiment) phenobarbital (PB, 500 ppm) added to a Torula yeast‐based diet containing 0.17 ppm of selenium. Dietary selenium (2 ppm), as sodium selenite, was given to Group B one week before and during DEN treatment, to Group C one week before and during PB treatment, and to Group D during the entire experiment. Groups A and E received the unsupplemented diet, whereas Group E was not treated with DEN or PB. Pair‐feeding conditions were used to minimize possible influences of differences in food intake and growth. Rats were killed at the 19th and 24th weeks after the experiment began. No significant differences were found in food and fluid intakes or in growth rates among the groups. Livers in Group E were histologically normal, whereas preneoplastic and neoplastic lesions were found in all other groups. In rats killed at the 19th and 24th weeks, the numerical and the volumetric densities of preneoplastic lesions did not differ significantly between all the groups. Similarly, the incidence of hepatocellular carcinomas only detected at 24 weeks was not significantly different between the groups. These results indicated that in this particular model of hepatocarcinogenesis, the dietary supplementation of 2 ppm of selenium did not modify the development of preneoplasia and carcinomas.     

Ethanol ingestion combined with lowered carbohydrate intake enhances the initiation of diethylnitrosamine liver carcinogenesis in rats.

The effect of ethanol on the initiation of diethylnitrosamine- (DEN) induced liver carcinogenesis was investigated in rats. In the first experiment, eight-week-old male Wistar rats were maintained on four liquid diets: a basal diet (Group 1), a low-carbohydrate (low-CHO) diet (Group 2), a basal diet+ethanol (Group 3), or a low-CHO diet+ethanol (Group 4). After three weeks on these diets, 50 mg/kg of DEN was injected intraperitoneally. The plasma glutamic-oxaloacetic transaminase activity in Group 4 was higher 24 hours after DEN administration than in Groups 1 and 3. The plasma glutamic-pyruvic transaminase activity in Groups 3 and 4 was higher than in Groups 1 and 2. The number of gamma-glutamyltranspeptidase-positive foci per unit liver area 41 weeks after DEN administration was higher in Group 4 than in Group 1. The area of gamma-glutamyltranspeptidase-positive foci was greater in Groups 2 and 4 than in Group 1. In the second experiment, Groups 1 and 4 were given DEN orally (25 or 75 mg/kg). Plasma glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase activities 24 hours after DEN administration were significantly higher in Group 4 than in Group 1, but only when the dose of DEN was 75 mg/kg. In contrast, the number and area of placental glutathione S-transferase-positive foci per unit liver area were greater in Group 4 than in Group 1 only after 25 mg/kg of DEN. Thus the severity of hepatotoxicity and the incidence of precancerous liver lesions were not necessarily correlated. These findings together indicate that a combination of ethanol and a low-CHO diet enhances DEN-induced liver carcinogenesis in rats by increasing the bioactivation of DEN in the liver.     

Inhibition by selenium of intrahepatic cholangiocarcinoma induction in Syrian golden hamsters by N'-nitrosobis(2-oxopropyl)amine.

The effects of selenium supplementation on induction of cholangiocarcinomas and related precancerous lesions in female Syrian Golden hamsters by N'-nitrosobis(2-oxopropyl)amine (BOP) were investigated. Four-week-old animals were divided into two groups according to the selenium level contained in the drinking water (0.1 ppm or 4.0 ppm) and fed a purified diet containing less than 0.05 ppm of the trace element. Starting at Week 4 of the experiment, hamsters were administered 10 weekly injections of BOP (10 mg/kg body wt) and then killed 18 weeks after the last carcinogen administration. Animals receiving physiological saline alone served as controls. Cholangiocellular carcinomas tended to be reduced, and putative preneoplastic lesions of cholangiofibrosis were significantly decreased in the high-as opposed to the low-selenium groups in terms of both incidence rate and number per effective animal. The respective high and low selenium values for incidence and number were 24/38% and 0.34/0.66, respectively, for cholangiocarcinomas and 50/89% and 1.21/8.44, respectively, for cholangiofibroses. Proliferation of intrahepatic bile ducts was also significantly inhibited in the high-selenium group along with cyst formation. Biochemical investigation revealed both selenium level and glutathione peroxidase activity to be significantly greater in the high-than in the low-selenium group livers. The results thus suggest that selenium may inhibit BOP-induction of bile duct lesions, possibly via glutathione peroxidase-mediated alteration of carcinogenesis.     

Lack of effect of dietary alpha-tocopherol on chemically induced hepatocarcinogenesis in rats

We investigated the effects of alpha-tocopherol on diethylnitrosamine (DEN) initiation-phenobarbital (PB) promotion of hepatic foci in female Sprague-Dawley rats. Groups of eight rats were initiated with DEN (15 mg/kg) at 24 hours of age. After weaning, they received diets containing 500 ppm PB and various concentrations of alpha-tocopherol, deficient (0 ppm), adequate (100 ppm), and supplemented (5,000 ppm), for 24 weeks. Rats fed alpha-tocopherol-supplemented diets had significantly greater hepatic alpha-tocopherol levels than those fed alpha-tocopherol-deficient or -adequate diets (p < 0.05). Liver lipid peroxidation (measured as thiobarbituric acid-reactive substances) was significantly greater in rats fed alpha-tocopherol-deficient diets than in those fed alpha-tocopherol-adequate or -supplemented diets (p < 0.05). The dietary alpha-tocopherol level had no significant effect on the ratios of reduced glutathione (GSH) to oxidized GSH or reduced GSH to total GSH in the liver or on the plasma prostaglandin E2 concentration or on the activities of hepatic cytosolic and particulate protein kinase C. Rats fed alpha-tocopherol-adequate or -supplemented diets had significantly greater hepatic glutathione S-transferase, GSH reductase, and GSH peroxidase activities than those fed alpha-tocopherol-deficient diets (p < 0.05). The dietary alpha-tocopherol level did not significantly affect the formation of hepatic gamma-glutamyl transpeptidase- and placental glutathione S-transferase-positive foci. These results suggest that alpha-tocopherol does not influence hepatic foci formation and that reactive oxygen species may not be the underlying mechanism of hepatic foci formation in this DEN initiation-PB promotion model of hepatocarcinogenesis.     

Suppression of altered hepatic foci development by a high fish oil diet compared with a high corn oil diet in rats

Effects of low corn oil, high corn oil, and high fish oil diets on altered hepatic foci development in female Sprague-Dawley rats were investigated. Rats assigned to Groups 1-4 were initiated with saline as the control and those assigned to Groups 5-7 were initiated with diethylnitrosamine (DEN 15 mg/kg) at 24 hours of age. After weaning, all rats, except those in Group 1, received 500 ppm phenobarbital (PB) in their diet as tumor promoter for three months. Altered hepatic foci development was significantly lower in DEN-initiated rats fed the high fish oil + PB diet than in DEN-initiated rats fed the high corn oil + PB diets. Liver weight and relative liver weight were significantly greater in rats fed the high fish oil + PB diet than in rats fed the other diets, and hepatic biotransformation/detoxification enzyme activities were greater in rats fed the fish oil + PB diets than in rats fed the other diets. These results suggest that the effect of a high fish oil diet on altered hepatic foci may occur through regulation of hepatic biotransformation/detoxification enzyme activities, leading to alteration in the tumor-promoting action of PB. Dietary lipid significantly affected the hepatic phospholipid fatty acid composition of rats. n-3 polyunsaturated fatty acids were incorporated into membrane phospholipid at the expense of n-6 polyunsaturated fatty acids. A high fish oil diet caused greater oxidative stress in rats, as measured by plasma vitamin E level, red blood cell glutathione status, liver lipid peroxidation, and hepatic glutathione reductase activity. Pearson's correlation analysis indicated that the foci number was negatively correlated to the liver thiobarbituric acid-reactive substance and 7-pentoxyresorufin O-dealkylase activity, and the foci area was negatively correlated to the liver thiobarbituric acid-reactive substance activity (p < 0.05) in rats of groups that developed foci. These results suggest that the type of dietary lipid is the more important determinant for gamma-glutamyl transpeptidase-positive foci development than the amount of dietary lipid when rats consumed approximately the same amount of calories in all the dietary groups, and the underlying mechanisms may be partially ascribed to the antioxidant/oxidation status and biotransformation/detoxification system of rats.     

Effects of fish oil and safflower oil emulsions on diet-induced hepatic steatosis in rats receiving total parenteral nutrition

This study was conducted to investigate the effects of fish oil and safflower oil emulsions in total parenteral nutrition (TPN) solutions on diet-induced hepatic steatosis. Rats were divided into a control group (C, n = 6) and four experimental groups (A, B, S, F, n = 11 approximately 14). The control group was fed a chow diet whereas the experimental groups received a high fat (15%, w/w) diet containing 0.1% (w/w) cholesterol. Group A received the high fat diet for 4 weeks, and was killed at the end of the fourth week to ensure that hepatic steatosis had occurred. Groups S and group F received TPN with safflower oil or fish oil emulsions, respectively, for 1 week following experimental diet feeding for 4 weeks. Group B was fed a limited amount of the high fat diet, without cholesterol, for 1 week following 4 weeks of experimental diet in order to maintain the same body weight and cholesterol intake as the TPN groups. Diet-induced hepatic steatosis was observed in the experimental groups. Fat deposition was reversed when the total caloric and cholesterol intake was reduced. Fish oil infusion ameliorated the severity of hepatic steatosis, whereas safflower oil had no effect on liver fat deposition. These results suggest that TPN with fish oil emulsions may be beneficial to patients with diet-induced hepatic steatosis.     

Effects of dietary selenium and vitamin E on hepatic mixed-function oxidase activities and in vivo covalent binding of aflatoxin B1 in rats

Male weanling fischer-344 rats were fed a selenium (Se)-vitamin E (VE) deficient Torula yeast basal diet or that diet supplemented with a graded levels of SE (0.2-6.0 ppm as Na2SeO3) or VE (100 iu/kg as all-rac-2-tocopheryl acetate), or both, for 4 or 6 weeks. Se deficiency and excess (6.0 ppm) markedly depressed in vivo covalent binding of aflatoxin (AFB1) to macromolecules in livers of rats killed 2 hours after an i.p. dose of 1 mg/kg tritiated AFB1. VE supplementation had no effect. Prior phenobarbital (PB) treatment generally decreased adducts without changing diet-related trends. Some hepatic enzyme capabilities were also measured. Cytochrome b5 content and cytochrome c reductase activity were unaffected by diet. VE increased cytochrome P-450 content, ethylmorphine N-demethylase and benz(alpha)pyrene hydroxylase activities; all these were unaffected by Se levels. Se deficiency and excess (but not VE deficiency) increased glucuronyl transferase. PB induction affected all diet groups and was more in agreement with MFO activity than transferase. Adduct formation was more consistently related to transferase activity than to MFO activities. The contrasting effects of SE and VE on AFB1 adducts in rats and chicks are discussed.     

Regression of experimental cancer by oral administration of combined alpha-tocopherol and beta-carotene

alpha-Tocopherol (vitamin E) and beta-carotene have been shown to be capable of regressing established epidermoid carcinomas of hamster buccal pouch when injected locally into the tumor site. Neither has yet been shown to be effective in regressing cancer when administered by oral route. However, a combination of both alpha-tocopherol and beta-carotene was shown to be effective in regressing epidermoid carcinomas of hamster buccal pouch when the mixture was administered orally in vegetable oil. The epidermoid carcinomas were induced in the right buccal pouch of 100 Syrian hamsters by painting three times weekly for 14 weeks with a 0.5% solution of 7,12-dimethylbenz[a]anthracene in mineral oil. The animals were then divided into five equal groups of 20 animals. Group 1 animals received no further treatment and represented tumor controls. Group 2 animals received 200 micrograms beta-carotene and 200 micrograms dl-alpha-tocopherol acid succinate combined in 0.2 ml vegetable oil. Animals received the mixture daily by mouth using a 1-ml syringe. Groups 3 and 4 received beta-carotene and alpha-tocopherol individually in double amounts (400 micrograms in 0.2 ml vegetable oil). Group 5 animals received only the vegetable oil (0.2 ml daily) and were controls for vehicle. The animals in Groups 1, 3, 4, and 5 were killed after 22 weeks because the tumors were extensive, large, and necrotic and the animals were weak and cachectic. After 22 weeks, the tumors in Group 2 animals were small in 15 out of 20 animals. The tumors were reduced in size compared with tumor burden at 14 weeks, the point at which the beta-carotene/alpha-tocopherol was started.     

Lack of effect of selenium on induction of tumors of esophagus and bladder in rats by two nitrosamines

The effect of differences in level of dietary selenium on the induction of esophageal and bladder tumors in rats by two nitrosamines was investigated. Groups of 20 female F344 rats were given a synthetic diet containing less than 0.05 ppm Se to which selenium (as sodium selenite) was added at the concentration of 0.35, 0.7, 1.4 and 2.1 ppm selenium. These four groups, plus one without added Se, were treated with 20 ml per rat per day, 5 days a week, of a solution of nitrosomethylcyclohexylamine containing 5 mg/liter. A parallel five groups were treated in the same way with a solution of nitrosomethyl-3-carboxypropylamine in drinking water containing 600 mg per liter, as drinking water. Treatment lasted 28 weeks, at which time some animals had developed tumors. A group of 20 rats fed 0, 1.4 and 2.1 ppm Se was not treated with carcinogen. Rats consuming 1.4 ppm or 2.1 ppm Se gained weight more slowly than other groups. There was no significant difference in survival between the five groups treated with each carcinogen but receiving different dietary levels of selenium. Neither was there any significant difference between groups receiving each carcinogen in the incidence of tumors of the esophagus induced by nitrosomethylcyclohexylamine or of tumors of the urinary bladder induced by nitrosomethylcarboxypropylamine. Control rats on the synthetic diets did not survive as well as untreated rats eating regular chow diet. In these conditions there was no effect of dietary selenium levels on the induction of tumors in female rats by the two carcinogenic nitrosamines we used.     

Regression of experimental cancer by oral administration of combined α‐tocopherol and β‐carotene

Abstract

α‐Tocopherol (vitamin E) and β‐carotene have been shown to be capable of regressing established epidermoid carcinomas of hamster buccal pouch when injected locally into the tumor site. Neither has yet been shown to be effective in regressing cancer when adminstered by oral route. However, a combination of both α‐tocopherol and β‐carotene was shown to be effective in regressing epidermoid carcinomas of hamster buccal pouch when the mixture was adminstered orally in vegetable oil.

The epidermoid carcinomas were induced in the right buccal pouch of 100 Syrian hamsters by painting three times weekly for 14 weeks with a 0.5% solution of 7,12‐dimethylbenz[a]an‐thracene in mineral oil. The animals were then divided into five equal groups of 20 animals. Group 1 animals received no further treatment and represented tumor controls. Group 2 animals received 200 μg β‐carotene and 200 μg dl‐α‐tocopherol acid succinate combined in 0.2 ml vegetable oil. Animals received the mixture daily by mouth using a 1 ‐ml syringe. Groups 3 and 4 received β‐carotene and α‐tocopherol individually in double amounts (400 μg in 0.2 ml vegetable oil). Group 5 animals received only the vegetable oil (0.2 ml daily) and were controls for vehicle. The animals in Groups 1,3,4, and 5 were killed after 22 weeks because the tumors were extensive, large, and necrotic and the animals were weak and cachectic. After 22 weeks, the tumors in Group 2 animals were small in 15 out of 20 animals. The tumors were reduced in size compared with tumor burden at 14 weeks, the point at which the β‐carotene/α‐tocopherol was started.     

Influence of acetaldehyde,dietary protein,carbon tetrachloride and butylatedhydroxytoluene on the toxicity of methylmercury in rats

The influence of environmental or dietary factors on the toxicity of methylmercury (MeHg) was investigated due to possibilities that humans exposed to methylmercury may have been sensitized. Groups of 8 rats were exposed to 0, 20 or 40 ppm MeHg in a semisynthetic diet and fed 0.5% BHT, 5% protein (instead of 15%), or injected with 250 mg/kg CCl₄, or acetaldehyde. In control rats neurotoxicity occurred at 4 weeks and 9 weeks with 40 and 20 ppm MeHg, respectively. Mortality was observed at 6 weeks with 40 ppm and 1 rat died in week 9 with 20 ppm MeHg. Acetaldehyde injected rats died at week 4 and 6 when fed 40 or 20 ppm MeHg. Neurotoxicity was observed in week 3 and 5 in these groups, respectively. Treating rats with the low protein or BHT accelerated neurotoxicity and mortality by 1 week with 40 ppm MeHg. These agents had killed all test animals within 7 weeks at 20 ppm MeHg. Neither acetaldehyde nor BHT influenced 0 ppm MeHg controls while 5% protein induced precipitous weight loss. In the case of CCl₄, the rats lived longer in combination experiments than one would have expected from the individual treatments.     

Enhancement of BOP-induced pancreatic carcinogenesis in selenium-fed Syrian golden hamsters under specific dietary conditions

We measured the effects of dietary selenium (Se) on pancreatic cancer induced in Syrian golden hamsters by N-nitrosobis(2-oxopropyl)amine (BOP). The animals were fed six experimental diets that contained different combinations of the following: 0.1, 2.5, or 5.0 ppm Se from sodium selenite or 2.5 ppm Se from D,L-selenomethionine in either a low (6.0%)- or high (24.4%)-fat diet. Se treatment was begun four weeks before BOP treatment, and the high-fat diet was fed from one week after the last BOP treatment. No evidence for inhibition of pancreatic cancer by Se was observed; in fact, with some experimental conditions, high-Se diets increased the pancreatic carcinoma yield. However, the dietary conditions needed for enhancement differed between the sexes. The male hamsters that received the high-fat diet containing 2.5 ppm Se had more carcinomas than did males given the 0.1 ppm Se level. Carcinoma yields in females did not differ between these diets. Females that received 2.5 ppm Se from D,L-selenomethionine had a greater pancreatic carcinoma yield that did those given 0.1 ppm Se diet. However, carcinoma yields did not differ in males fed these diets. Acinar cell nodule yields were generally reduced in hamsters given the high-Se diets, especially when Se levels in the high-fat diets were compared. Prefeeding 0.1 or 2.5 ppm Se did not influence the elution constants of pancreatic DNA from ductal cells, indicating no effect of Se on the repair of BOP-induced, single-strand breaks in DNA from these cells. Measurements in acinar cells suggested a more rapid repair of single-strand breaks in hamsters prefed 2.5 ppm Se than in those prefed 0.1 ppm Se.     

Effect of palm vitamin E on the healing of ethanol-induced gastric injury in rats

The effect of palm vitamin E on the healing of ethanol-induced gastric lesions and various biochemical parameters were investigated. The study was divided into two phases. In the first phase of the study, 42 rats of Sprague Dawley species (200–250 gm weight) were randomly divided into two groups fed with a normal diet (control) or palm vitamin E enriched diet (150 mg/kg) for 3 weeks. The rats were killed after 3 weeks of feeding. Gastric tissue contents of malondialdehyde (MDA), prostaglandin E 2 and acid were measured. In the second phase of the study 42 rats were divided into two groups. Group 1 was fed normal rat pellets (control) and group 2 was fed palm vitamin E enriched pellets (150 mg/kg food) for 3 weeks. After 3 weeks of feeding gastric mucosal injury was induced by an orogastric tube administration of 0.5 ml 100% ethanol. The rats were killed at 1 hour, 4 hours and 1 week after ethanol exposure for semiquantitative determination of ulcer index and gastric acid concentration. Gastric tissue MDA and muscus were measured only at 1 week after ethanol exposure. In the first phase of the study we found that palm vitamin E only caused a significant reduction in gastric MDA. However, it showed no significant effects on prostaglandin E 2 and gastric acid concentration. In the second phase of the study, the mean ulcer index of palm vitamin E supplemented group killed after 1 week of ethanol exposure was significantly lower compared to the respective control. However, there was no significant difference in ulcer index in rats killed at 1 hour and 24 hours after ethanol exposure. The gastric acid concentration was significantly higher in the group treated with palm vitamin E killed 1 week after ethanol exposure compared to control. The gastric tissue MDA was significantly lower in the palm vitamin E supplemented group compared to control. There was no significant difference in gastric mucus content of the both groups. The ulcer healing which occurred in the presence of a high gastric acid suggests that the effect of palm vitamin E on the healing of gastric lesions was not mediated via a reduction in gastric acid nor was it mediated through increasing prostaglandin E 2 or mucus production. The most probable mechanism is via reducing lipid peroxidation as reflected by a significant decreased in gastric tissue MDA content.     

A semipurified diet that suppresses phenobarbital promotion of hepatocarcinogenesis in the rat

Six groups of F344/N female rats were fed either a modified AIN‐76 diet (20% casein, 5 % corn oil, 65% cornstarch, 5% cellulose) (AIN) or a diet formulated by Dr. M. Pariza (PD) (30% casein, 10% partially hydrogenated corn oil, 40% sucrose, 15% cornstarch) beginning four days before 70% partial hepatectomy. One day after the surgery, one group fed each diet was intubated with 10 mg/kg diethylnitrosamine (DEN). One week later, these groups plus one control group fed each diet were given 0.05% phenobarbital in the diet for 6 or 14 months. After the rats were killed, blocks of liver tissue were frozen on dry ice and stored at — 70°C. Three frozen serial sections were stained for γ‐glutamyltransferase, ATPase, and glucose‐6‐phosphatase.

Numbers and volume of altered hepatic foci (AHF) were analyzed by stereological techniques. After 14 months of feeding these regimens, rats initiated with DEN and fed the AIN + PB had significantly greater numbers and a higher percent volume of the liver of most phenotypes of AHF than all other groups, including those fed PD + PB following initiation with DEN. The numbers of AHF exhibiting more complex phenotypes (i.e., scored by more than one marker) remained unaltered between 6 and 14 months. These findings indicate that the effectiveness of PB as a promoting agent in multistage hepatocarcinogenesis is significantly altered when fed with two different diets of known composition. Therefore, dietary composition can be a significant factor in studies of the stage of promotion in hepatocarcinogenesis.     

儿茶素抑制二甲基肼诱发小鼠大肠癌的实验研究

昆明种小鼠随机分成７组，１～５组小鼠皮下注射二甲基肼（１，２－Ｄｉｍｅｔｈｙｌｈｙｄｒａｚｉｎｅ，ＤＭＨ），剂量２０ｍｇ／ｋｇｂｗ，每周一次，连续２０周。第２～５组于注射前一周开始灌胃儿茶素，每鼠每日分别为１ｍｇ、２ｍｇ、４ｍｇ、没食子酰表没食子儿茶素［（－）－Ｅｐｉｇａｌｌｏ－ｃａｔｅｃｈｉｎｇａｌｌａｔｅ］２ｍｇ，第６组给儿茶素３ｍｇ作为对照组，每周连续５次至２３周。第７组为溶剂对照组。２７周处死小鼠，结果显示：两组对照组小鼠未发现肿瘤。ＤＭＨ组大肠癌发生率为８０％，与２～５组比较明显升高（Ｐ＜０．００１），结果提示：（１）不同剂量的儿茶素都具有防癌作用，其机理可能与诱导ＳＯＤ等抗氧化剂的活性消除有害自由基有关；（２）其抑癌有效成分可能是多种儿茶素协同作用的结果；（３）儿茶素对个鼠无毒性作用。     

A semipurified diet that suppresses phenobarbital promotion of hepatocarcinogenesis in the rat

Six groups of F344/N female rats were fed either a modified AIN-76 diet (20% casein, 5% corn oil, 65% cornstarch, 5% cellulose) (AIN) or a diet formulated by Dr. M. Pariza (PD) (30% casein, 10% partially hydrogenated corn oil, 40% sucrose, 15% cornstarch) beginning four days before 70% partial hepatectomy. One day after the surgery, one group fed each diet was intubated with 10 mg/kg diethylnitrosamine (DEN). One week later, these groups plus one control group fed each diet were given 0.05% phenobarbital in the diet for 6 or 14 months. After the rats were killed, blocks of liver tissue were frozen on dry ice and stored at -70 degrees C. Three frozen serial sections were stained for gamma-glutamyltransferase, ATPase, and glucose-6-phosphatase. Numbers and volume of altered hepatic foci (AHF) were analyzed by stereological techniques. After 14 months of feeding these regimens, rats initiated with DEN and fed the AIN + PB had significantly greater numbers and a higher percent volume of the liver of most phenotypes of AHF than all other groups, including those fed PD + PB following initiation with DEN. The numbers of AHF exhibiting more complex phenotypes (i.e., scored by more than one marker) remained unaltered between 6 and 14 months. These findings indicate that the effectiveness of PB as a promoting agent in multistage hepatocarcinogenesis is significantly altered when fed with two different diets of known composition. Therefore, dietary composition can be a significant factor in studies of the stage of promotion in hepatocarcinogenesis.     

Inhibition of 7,12-dimethylbenz[a]anthracene-induced lipid peroxidation and mammary tumor development in rats by vitamin E in conjunction with selenium.

The effects of combined dietary vitamin E supplementation and a relatively low increase in selenium levels on 7,12-dimethylbenz[a]anthracene (DMBA) induction of lipid peroxidation in the short term and development of mammary tumors in the long term were investigated in female Sprague-Dawley rats. Control animals were fed the basal diet (20 mg/kg vitamin E and 0.6 mg/kg selenium) throughout the experiment. Three other groups received a high vitamin E diet (235 mg/kg vitamin E and 0.6 mg/kg selenium) at different times, the first two from three weeks after DMBA treatment and the other throughout the experiment. When the vitamin E diet with selenium supplementation was applied until three weeks after DMBA or until the termination of the experiment, tumor yields (tumors per rat) were significantly inhibited compared with the control group. On the other hand, delaying the supplementation of vitamin E until three weeks postcarcinogen produced no prophylactic effect. The elevation of lipid peroxidation levels observed immediately after DMBA administration was also significantly inhibited in both mammary fat pads and livers of animals in the high vitamin E group. It was therefore concluded that the inhibitory effect of vitamin E in combination with selenium on tumorigenesis might be causally related to reduction of carcinogen treatment associated with lipid peroxidation, the latter presumably playing an important role in DMBA-induced mammary carcinogenesis.     

Inhibition of 7,12‐dimethylbenz[a] anthracene‐induced lipid peroxidation and mammary tumor development in rats by vitamin e in conjunction with selenium

The effects of combined dietary vitamin E supplementation and a relatively low increase in selenium levels on 7,12‐dimethylbenz[a]anthracene (DMBA) induction of lipid peroxidation in the short term and development of mammary tumors in the long term were investigated in female Sprague‐Dawley rats. Control animals were fed the basal diet (20 mg/kg vitamin E and 0.6 mg/kg selenium) throughout the experiment. Three other groups received a high vitamin E diet (235 mg/kg vitamin E and 0.6 mg/kg selenium) at different times, the first two from three weeks after DMBA treatment and the other throughout the experiment. When the vitamin E diet with selenium supplementation was applied until three weeks after DMBA or until the termination of the experiment, tumor yields (tumors per rat) were significantly inhibited compared with the control group. On the other hand, delaying the supplementation of vitamin E until three weeks postcarcinogen produced no prophylactic effect. The elevation of lipid peroxidation levels observed immediately after DMBA administration was also significantly inhibited in both mammary fat pads and livers of animals in the high vitamin E group. It was therefore concluded that the inhibitory effect of vitamin E in combination with selenium on tumorigenesis might be causally related to reduction of carcinogen treatment associated with lipid peroxidation, the latter presumably playing an important role in DMBA‐induced mammary carcinogenesis.     

Lead attenuates the antipunishment effects of ethanol

Adult male rats were exposed to a diet containing no added chemicals, or a diet containing 500 ppm added lead (as lead acetate), for 70 days. On Day 71 (training day), after 24 h of water deprivation, all animals were placed in a test apparatus and permitted to make 220 licks for a 5.5 percent (v/v) sucrose in water solution. On Day 72 (test day), all animals received conditioned punishment training where electric shock was delivered to the tongue following every 20 licks of the sucrose and water solution. Prior to commencing punishment training on Day 72, half the animals for the control diet condition (Group Control-Diet-Saline), and half the animals for the lead diet condition (Group Lead-Diet-Saline), received IP injections of saline. Conversely, the remaining half of the animals (Groups Control-Diet-Ethanol and Lead-Diet-Ethanol) received IP injections of 1.5 g/kg ethanol. The results of the conditioned punishment test revealed that animals exposed to a control diet and administered ethanol (Group Control-Diet-Ethanol) engaged in more punished licking and received more shocks than their lead-treated counterparts (Group Lead-Diet-Ethanol). Both of the groups exhibited more punished licking and received more shocks than either of the groups that received saline injections. The possibility that lead contamination may reduce the pharmacologic impact of ethanol is noted.     

Appreciation of selenium concentration in blood and tissues of male rat as a result of diet ingredients changes and its supplementation with chosen group B vitamins

The influence of diet ingredients and its supplementation with chosen B group vitamins on concentration of selenium in blood serum and tissues and activity of glutathione peroxidase in blood and liver of male rats was examined in the conducted experiment. The animals, aged 5 months, were divided into three groups and fed ad libitum with granulated mixes. Group I with basic mix containing among other things full grains, Group II with modified mix in which full grains were exchanged for wheat flour and in part with saccharose and Group III with modified mix supplemented in excess with vitamins B1, B2, B6 and PP. The experiment was conducted for six weeks during which the amount of consumed feeding stuff was calculated currently and once a week body mass of the animals was checked. When the experiment was finished the activity of GSH-Px was determined by spectrophotometric method in blood and liver whereas concentration of selenium in blood serum, muscles and in liver by fluorometric method. It was ascertained that the change of diet ingredients and its supplementation with chosen group B vitamins was in favour of lowering the amount of selenium in the examined tissues, and the decrease was not only the result of lower amount of the consumed element, but also of its increased usage, forced by the changes taking place under the influence of diet components and its supplementation.