MPTP in mice: treatment, distribution and possible source of contamination.

Mice were treated daily with [3H]MPTP (30 mg/kg, 1 uCi, s.c.) for 1, 3, and 10 days to determine the fate and localization of tritiated compounds. An untreated mouse was housed either in the same cage ("cage-mate control") or in an adjacent cage separated by mesh-wire ("near-neighbor control"). The radioactivity measured in blood, brain, liver, and remaining body of [3H]MPTP-treated mice was dependent on the total dose of the drug the animals received and did not vary with the type of tissue analyzed. Significant amounts of radioactivity were found in the tissues of the "cage-mate control" mice, but not of the "near-neighbor control" mice. The route of transmission appears to be through the urine, as the urine of [3H]MPTP-treated mice was highly radioactive after the drug injection. Only traces of radioactivity were found in their feces and there was no increase in the background radiation in the environment of the cages, indicating that the tritiated compounds were not exhaled. Proper disposal of urinary products of MPTP-treated animals is therefore necessary to reduce the risk of possible drug contamination in humans.

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.

Effects of dietary selenium on bis(2-oxopropyl)nitrosamine-induced carcinogenesis in Syrian golden hamsters.

In studies designed to determine the influence of dietary Se on pancreatic carcinogenesis, Syrian golden hamsters were fed unsupplemented torula yeast diet or diet supplemented with 0.1 or 5.0 ppm Se, from sodium selenite, starting at 4 weeks of age until the termination of the study. In separate groups, hamsters were given the diet supplemented with 0.1 ppm Se until 5 days after carcinogen treatment. Then they were fed either the unsupplemented diet or the diet supplemented with 5.0 ppm Se until the end of the experiment. N-Nitrosobis(2-oxopropyl)amine (BOP; CAS; 60599-38-4) treatment was given as a single sc injection of 20 mg/kg (body wt) at 8 weeks of age, and surviving hamsters were killed 50 weeks later. As a measure of Se status, glutathione peroxidase (GSHPX) activities were determined in plasma, erythrocytes, and liver. Values were elevated in animals fed higher levels of dietary Se. BOP treatment depressed plasma GSHPX at 24 hours and elevated erythrocyte and liver values at 4 weeks. Pancreatic ductular adenoma yields were inhibited with each elevation of dietary Se in female hamsters fed the diets, both before and after BOP administration, and were further inhibited in females that were fed diets containing 0.1 ppm Se before BOP administration and that were changed to the unsupplemented or 5.0-ppm-supplemented diets after BOP was given. Pancreatic ductular adenoma yields were highest in all male groups given diets of 0.1 ppm Se before BOP administration, irrespective of the Se level after BOP was fed. Adenoma yields in males were lowest in hamsters fed unsupplemented diet, both before and after BOP treatment. Pancreatic carcinoma yields were low and not influenced by dietary Se. The incidence of hepatic necrosis was elevated in BOP-treated hamsters fed the unsupplemented diet, and that of biliary cystic adenomas was highest in the group fed 0.1 ppm Se before and after BOP treatment.

Tolerance of low and high dietary selenium throughout the life span of Syrian hamsters.

In lifetime studies on the effects of dietary selenium (Se) levels, Syrian hamsters were fed diets containing low (unsupplemented torula yeast), adequate (0.1 ppm Se supplemented from sodium selenite), or excessive (5 ppm Se supplemented from sodium selenite) levels of Se. A commercial ration was fed to separate groups. Male and female hamsters were assigned to each diet, and blood samples were collected at 54 and 79 weeks of age for determination of Se status. Body weights of male hamsters were generally highest in those fed unsupplemented diets and lowest in those fed 5 ppm Se supplements. Female weights did not differ between the three semipurified diets. Erythrocyte and plasma glutathione peroxidase and blood Se values increased with the increments in dietary Se at the 54- and 79-week measurements. Survival was approximately 40-45% lower in hamsters fed the commercial ration than in those fed semipurified diets, but was not altered by the Se level in the semipurified diet.

Tolerance of diets deficient or excessive in selenium by Syrian hamsters.

Syrian hamsters were fed torula yeast (TY) diets with 8 selenium (Se) supplement levels (0.0-10.0 ppm Se as sodium selenite) or casein (C) diets with 5 supplement levels (0.0-5.0 ppm Se as sodium selenite) for 25 weeks. Whole blood Se, plasma glutathione peroxidase (GSH-Px) activity and erythrocyte GSH-Px activity were measured after 5, 10, 15 and 25 weeks. At 25 weeks hematology was examined and tissue samples analyzed for Se and evaluated for histopathological lesions. While survival was not influenced by dietary Se, food consumption and body weight gain were altered in animals given TY, as those fed 0.0, 0.05 or 10.0 ppm Se consumed less diet. Weight gains at 25 weeks were highest in animals at the 0.1 ppm Se level and reduced in those given unsupplemented TY or 10.0 ppm Se supplements. Hemoglobin, hematocrit and red blood cell counts were reduced in females fed the lowest and highest Se supplements with TY diets. With both C and TY, whole blood Se rose with increasing dietary Se and in the case of TY, Se was elevated with each feeding increment, except between the 0.05 and 0.1 ppm or the 0.25 and 0.5 ppm levels. Plasma GSH-Px increased with rising Se up to 10 ppm, and erythrocyte GSH-Px activity increased up to 5 ppm Se. Erythrocyte GSH-Px values were higher in animals fed C diets. Histopathological observations were normal at all Se levels. Syrian hamsters tolerated dietary Se from 0.05 to 5.0 ppm Se for 25 weeks of observation without detrimental effects.