Role of fatty acyl coenzyme A oxidase in the efflux of oxidized glutathione from perfused livers of rats treated with the peroxisome proliferator nafenopin.

The diffusion of H2O2 into the cytoplasm from peroxisomes during high rates of peroxisomal beta oxidation of fatty acids was studied in perfused livers from rats treated with the hepatocarcinogenic peroxisome proliferator, nafenopin. Efflux of oxidized glutathione (GSSG) into the bile was used as a measure of increased H2O2 supply for cytoplasmic glutathione peroxidase. Male F-344 rats were given methylcellulose vehicle or nafenopin (80 mg/kg/day) by gavage for 5-8 days and livers perfused in situ with Krebs-Henseleit buffer containing 50 microM taurocholate and 0.

Carcinogen treatment increases glutathione hydrolysis by gamma-glutamyl transpeptidase.

The effect of carcinogen treatment on gamma-glutamyl transpeptidase (GGT)-mediated hydrolysis of GSH to glutamate and cysteinylglycine in the blood and bile compartments was investigated in livers perfused in situ. Treatment of rats with 40 p.p.

In vivo studies on the mechanism of di(2-ethylhexyl)phthalate carcinogenesis.

In a study sponsored by the National Toxicology Program, di(2-ethylhexyl)phthalate (DEHP) fed in the diet at 1.2% significantly increased the incidence of female rats with hepatocellular carcinomas. Extensive evaluation of DEHP for carcinogenicity has yielded negative results.

Di(2-ethylhexyl)phthalate: lack of initiating activity in the liver of female F-344 rats.

Di(2-ethylhexyl)phthalate (DEHP) is a peroxisome proliferator that was hepatocarcinogenic in female rats in a National Toxicology Program 2-year bioassay. However, DEHP was negative for promotional activity when tested using the same sex and strain of rat and dosing regimen that resulted in hepatocarcinogenicity. The carcinogenic response of peroxisome proliferators may be related to excess production of reactive oxygen species in the cell.

Quantitative evaluation of hepatic foci of cellular alteration occurring spontaneously in Fischer-344 rats.

Stereologic procedures were used to quantitate spontaneously occurring liver foci of altered staining in control Fischer-344 rats at 33, 59, 85, and 111 weeks of age. Foci were identified using hematoxylin and eosin stained sections. In both males and females, foci were first observed at 59 weeks.

Lack of hepatic promotional activity by the peroxisomal proliferating hepatocarcinogen di(2-ethylhexyl)phthalate.

The hepatocarcinogenicity of di(2-ethylhexyl)phthalate (DEHP) was demonstrated in a recent bioassay in both rats and mice. Due to the negative genotoxicity of DEHP in both in vivo and in vitro assays, it was hypothesized that the positive carcinogenic response of DEHP may have been due to a promotional effect of DEHP on spontaneous foci. However, when DEHP was used in the promotion phase of a rat hepatic initiation-promotion system, no promotional activity could be demonstrated after either 3 or 6 months of feeding DEHP at a dietary concentration of 1.