Increase in hepatic gamma-glutamyltransferase (GGT) activity following chronic ethanol intake in combination with a high fat diet.

Increased hepatic gamma-glutamyltransferase (GGT) activity following chronic ethanol consumption has been attributed to enzyme induction, dietary carbohydrate imbalance, and/or to hepatic cell damage. In this study, hepatic GGT activity was increased in rats consuming ethanol (35% of kcals) in a high fat (35% of kcals) diet compared to pair fed and ad lib. fed high fat controls (P less than or equal to 0.01), but no enhancement of activity was observed in those rats consuming ethanol on low fat (11% of kcals) diets. The high-fat-ethanol group also had increased hepatic lipid (P less than or equal to 0.01) and decreased glutathione levels (P less than or equal to 0.05) compared to their ad lib. fed control group. In rats that had ethanol removed from their diet for the final 4 weeks of the 12-week dietary treatment period, levels of GGT, lipid or glutathione were not different from control values. Histochemical evaluation of hepatic GGT activity showed increases associated with centrolobular lipid accumulation in ethanol-fed rats consuming a high fat diet. The cause of the increase in hepatic GGT activity could not be determined from this experiment. However, increased microsomal enzyme activity did not appear to be related to GGT activity. It is suggested that cellular damage following increased lipid accumulation, depletion of hepatic glutathione, or changes in biliary flow may be associated with the increased GGT activity.

Effect of ethanol consumed in combination with high or low fat diets on the postinitiation phase of hepatocarcinogenesis in the rat.

In this study, the effect of chronic ethanol ingestion on the modification of the postinitiation phase of hepatocarcinogenesis was examined. Hepatic lesions were initiated in Sprague-Dawley rats by administration of 10 doses of aflatoxin B1 (AFB1) over a 2-week period. Following a week of acclimation rats were fed ethanol (35% of caloric intake) in low fat (11% of calories) or high fat (35% of calories) AIN-76-based liquid diets according to a unique feeding regime for 12 weeks. The effect of ethanol on the development of hepatic gamma-glutamyltransferase (GGT)-positive foci and on nutrient status was evaluated. Only those rats consuming ethanol with a high fat diet developed fatty livers, but all those consuming ethanol had low hepatic vitamin A and glutathione levels compared to pair-fed and ad libitum-fed controls. Despite these changes, no effect of ethanol consumption on the formation of GGT-positive foci was observed. Rats fed a high fat diet had an increased number and size of foci compared to rats on a low fat diet (P less than or equal to 0.01). It was concluded that despite these effects of ethanol on several physiological parameters, modification of the development of presumptive preneoplastic hepatic foci was not affected.

Changes in preneoplastic response to aflatoxin B1 in rats fed green beans, beets or squash.

Weanling male Fischer rats were fed diets containing 25% freeze-dried green beans, beets or squash either with or without 1 ppm aflatoxin B1 for 8 wk. Plasma alpha-foetoprotein concentrations were determined weekly from wk 4 to 7. During wk 8 the animals were killed and hepatic sections were stained for gamma-glutamyl transpeptidase. All three vegetable diets, as compared to the basal semi-purified diet, enhanced both aflatoxin-B1-induced elevation of plasma alpha-foetoprotein and aflatoxin-B1-induced emergence of hepatic cell foci of gamma-glutamyl transpeptidase. The data suggest that these vegetables contain natural factors that enhance aflatoxin B1 carcinogenicity.

Enhancement of plasma alpha-fetoprotein, as measured by sandwich-type radioimmunoassay, and induction of gamma-glutamyl transpeptidase-positive hepatic cell foci in rats fed benzo[a]pyrene.

Male Fischer rats were fed semipurified diets containing 0, 1, 100, and 1000 ppm benzo[a]pyrene (BaP) for 6 or 13 wk. Plasma samples were assayed for alpha-fetoprotein (AFP) by a new sandwich-type radioimmunoassay (RIA) utilizing a special controlled porous-glass solid phase. This procedure is described in detail. Significant AFP elevation (p less than or equal to 0.01) was observed in the highest BaP treatment group after 5 wk of treatment. The 1 and 100 ppm Bap groups exhibited no AFP elevation throughout the study. Liver sections from the 1000 ppm groups had discrete gamma-glutamyl transpeptidase (GGT)-positive foci 10-20 cells in diameter by the 6th wk. GGT-positive foci were not evident in liver sections from the other treatment groups. Thus a high level of dietary BaP appears to rapidly alter rat liver cells, indicating hepatic neoplasia.

Plasma alpha-fetoprotein elevation and mutagenicity of urine as early predictors of carcinogenecity in benzo(alpha)pyrene fed rats.

Weaning male Fischer rats were fed purified diets containing 0, 1, 100, or 1,000 ppm benzo(alpha)pyrene (BAP) for 6 weeks or 0, 1, or 100 ppm BAP for 3 weeks, then the same diets with or without 500 ppm sodium phenobarbital (PB) for an additional 5 weeks. Blood plasma alpha-fetoprotein (AFP) was determined at one to two week intervals. Urine, collected for eight hours during the sixth or eighth week of treatment, was tested for mutagenicity with S. typhimurium strain TA98 by the Salmonella/mammalian microsome test. Frozen liver sections were stained for gamma-glutamyl transpeptidase (GGT) activity. Only the 1000 ppm BAP treatment induced elevated blood plasma levels of AFP and GGT-positive hepatic cell foci. Urine from rats fed 1000 ppm BAP pr 100 ppm BAP + 500 ppm PB caused a significant (P less than or equal to .05) increase in revertants of S. typhimurium, compared to urine from control rats. Evidence from this investigation suggests that plasma AFP determination and urinary mutagenesis testing could be useful in short term in vivo screening for potential carcinogens.