Effects of Simultaneous Dietary Exposure to 2,2′,4,4′,5,5′-Hexabromobiphenyl and 3,3′,4,4′,5,5′-Hexachlorobiphenyl on Hepatic Tumor Promotion in Rats

1989 ◽  
Vol 8 (6) ◽  
pp. 1201-1206 ◽  
Author(s):  
M. G. Evans ◽  
S. D. Sleight

Female Sprague-Dawley rats were partially hepatectomized, initiated with diethylnitrosamine (DEN), and fed diets containing 2,2′,4,4′,5,5′-hexabromobiphenyl (245-HBB), 3,3′,4,4′,5,5′-hexachlorobiphenyl (345-HCB), or combinations of 245-HBB and 345-HCB to determine the tumor-promoting ability of these compounds in a two-stage (initiation/promotion) hepatocar-cinogenesis system. Tumor-promoting ability was assessed by measuring hepatic foci positive for gamma glutamyl transpeptidase (GGT) activity. Concentrations of 10 or 100 mg 245-HBB/kg of diet caused significantly increased numbers of GGT-positive hepatic foci. When 245-HBB and 345-HCB were fed simultaneously, an additive effect on tumor-promoting ability was observed at dietary concentrations of 10 mg/kg 245-HBB and 0.1 mg/kg 345-HCB. However, an inhibitory effect on tumor promotion occurred when dietary concentrations of 100 mg/kg 245-HBB and 1.0 mg/kg 345-HCB were fed simultaneously. These results suggest that the tumor-promoting ability of simultaneous exposure to 245-HBB and 345-HCB can be additive or inhibitory depending upon the concentration of each congener in the diet.

1988 ◽  
Vol 7 (5) ◽  
pp. 687-697 ◽  
Author(s):  
D. Dixon ◽  
S.D. Sleight ◽  
S.D. Aust ◽  
M.S. Rezabek

Female, 180–200 g Sprague-Dawley rats were used to determine if 3,4,3',4'-tetrabromobi-phenyl (34-TBB) is a promoter or initiator in a two-stage hepatocarcinogenesis assay. To test for promotion, rats were partially hepatectomized (PH) 24 hr before initiation (day 1) with 10 mg of diethylnitrosamine (DEN)/kg body weight given intraperitoneally (IP). Thirty days later, promotion was with 34-TBB (0.1,1 or 5 mg/kg) or phenobarbital (PB) (500 mg/kg) in diets for 180 days. To test for initiation, rats were PH and were initiated on day 1 with 34-TBB (1, 5, or 10 mg/kg) orally or DEN (10 mg/kg) IP. On day 31, promotion was with 500 mg of PB/kg of diet for 180 days. Noninitiated and non-PH rats were used to assess the histological and ultrastructural tissue changes associated with administration of 34-TBB in the diet for 180 days. Tumor promotion-initiation were assessed by counting and measuring hepatic enzyme-altered foci (EAF) with gamma-glutamyl transpeptidase (GGT) activity. Congener 34-TBB acts as a promoter in experimental hepatocarcinogenesis in rats, as evidenced by increased numbers of GGT-positive EAF. Also, 34-TBB may have initiation potential, as suggested by increased numbers of EAF in rats initiated with 34-TBB and promoted by PB. Dietary administration of 34-TBB for 180 days is not severely toxic in rats, as evidenced by mild histological and ultrastructural changes and minimal alterations in organ and body weights. Congener 34-TBB does not accumulate in liver and adipose tissue of rats.


1990 ◽  
Vol 11 (11) ◽  
pp. 2015-2019 ◽  
Author(s):  
Toshiyuki Takata ◽  
Toshiyuki Minoura ◽  
Hideho Takada ◽  
Michitomo Sakaguchi ◽  
Manabu Yamamura ◽  
...  

1977 ◽  
Vol 232 (4) ◽  
pp. F335-F340 ◽  
Author(s):  
J. D. Wallin ◽  
R. A. Kaplan

Mechanisms for the concentrating defect produced by fluoride were examined in the rat. Free-water clearance at all levels of delivery was normal after 5 days of chronic fluoride administration in the hereditary hypothalamic diabetes insipidus rat. In the Sprague-Dawley rats, during moderate fluoride administration (120 micronmol/kg per day), urine osmolality and cyclic AMP excretion decreased and urine volume increased, but after exogenous vasopressin, volume decreased and osmolality and cyclic AMP increased appropriately. During larger daily doses of fluoride (240 micronmol/kg per day) urinary osmolality and cyclic AMP decreased and volume increased, which was similar to the changes seen during lower fluoride dosages, but these parameters did not change after exogenous vasopressin. These data suggest that ascending limb chloride reabsorption is unaltered by fluoride administration; in the presence of sufficient fluoride, collecting tubular cells apparently do not generate cyclic AMP or increase permeability appropriately in response to vasopressin. The postulated defect is felt to be due to either a decrease in ATP availability or to a direct inhibitory effect of fluoride on the vasopressin-dependent cyclic AMP generating system.


2013 ◽  
Vol 60 ◽  
pp. 297-301 ◽  
Author(s):  
R. Ebabe Elle ◽  
S. Gaillet ◽  
J. Vidé ◽  
C. Romain ◽  
C. Lauret ◽  
...  

1978 ◽  
Vol 64 (2) ◽  
pp. 131-142 ◽  
Author(s):  
Silvio Fiala ◽  
Babulal Pragani ◽  
Melvin D. Reuber

Adult male Sprague Dawley rats on which end-to-side portacaval shunt (PCS) operation was performed did not develop hyperplastic nodules and hepatomas when they were fed 3'-methyl-4-dimethylaminoazobenzene in semisynthetic basal diet for periods of up to 169 days. In contrast, all the intact rats fed the same diet for only 75 days, developed hyperplastic nodules in the liver. Transferred to normal pellet for another 25 days, hepatomas developed in 100% of these animals. The amount of protein-bond 3'-Me-DAB was found to be much smaller in operated rats than in intact animals. The glutathione (GSH) level in PCS-operated rats was lower than in intact controls. A single large dose of 3'-Me-DAB led to the increase of only about 30% in the concentration of GSH during the period of 24–48 h, compared to the increase of 50–100% in non-operated rats. No clear tendency to a gradual increase in the activity of γ-glutamyl transpeptidase was noted in PCS-operated rats during the period of 5% months of 3'-Me-DAB feeding. The increase in GT-ase activity never exceeded 30% above the level of GT-ase in the livers of PCS-operated rats fed basal diet without the carcinogen. This striking inhibition of GT-ase increase induced by 3'-Me-DAB in PCS-operated rats contrasted with an increase of GT-ase activity by 5,000% found in livers of non-operated rats with hyperplastic nodules after 75 days of 3'-Me-DAB feeding and the increase by up to 10,000% in developed hepatomas. These effects and the inhibition of 3'-Me-DAB-induced hepatocarcinogenesis, manifested by lack of preneoplastic morphologic changes and the absence of hepatomas in rats after PCS, can best be explained by functional deficiency of the liver to metabolize the procarcinogen 3'-Me-DAB into an activated carcinogen.


Toxicology ◽  
2012 ◽  
Vol 293 (1-3) ◽  
pp. 30-40 ◽  
Author(s):  
Clifford R. Elcombe ◽  
Barbara M. Elcombe ◽  
John R. Foster ◽  
Shu-Ching Chang ◽  
David J. Ehresman ◽  
...  

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