Hepatic glutathione S-transferase activity and aflatoxin B1-induced enzyme altered foci in rats fed fractions of brussels sprouts.

The aim of the present study was to determine whether the liver cytosol detoxication enzymes, glutathione S-transferases (GSTases) as well as gamma-glutamyl transpeptidase (GGT) foci induced by aflatoxin B1 (AFB) were changed by feeding weanling rats diets containing brussels sprouts, a glucosinolate fraction of brussels sprouts (extract), or a non-glucosinolate fraction (residue). All 3 of these diets induced high levels of hepatic GSTase specific activity as compared to purified-basal diet fed control rats. The brussels sprouts and the extract treatments, but not the residue dietary treatment, inhibited hepatic GGT foci induced by AFB. Thus, glucosinolates and non-glucosinolate fractions of brussels sprouts induce hepatic enzymes involved in detoxication mechanisms but the non-glucosinolate compound(s) apparently are not involved in all chemical carcinogen metabolic processes.

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.

Modification of beet and cabbage diets of aflatoxin B1-induced rat plasma alpha-foetoprotein elevation, hepatic tumorigenesis, and mutagenicity of urine.

Weanling male Fischer rats were fed a purified diet or diets containing 25% (w/w) freeze-dried ground beets or cabbage with or without 1 ppm aflatoxin B1 (AFB1) for 26 wk. In 3-7 wk the cabbage diet diminished, while the beet diet enhanced AFB1-induced plasma alpha-foetoprotein (AFP) elevation. When the experiment was extended to 42 wk by maintaining the animals on the purified (basal) diet for a further 16 wk the rats that had consumed AFB1 in the beet diet had 72 +/- 14 tumours/liver (mean surface diameter of tumours, 6.13 +/0 4.69 mm); animals that had been given AFB1 in the control diet had 30 +/- 16 tumours/liver (mean surface diameter, 4.36 +/- 3.16 mm); rats that had been given AFB1 in the cabbage diet had 13 +/- 5 tumours/liver (mean surface diameter, 4.28 +/- 2.89 mm). In the Salmonella/mammalian microsomal test, urine from rats fed AFB1 with beets caused significantly (P less than 0.05) more revertants in Salmonella typhimurium strain TA98 than did urine from rats fed AFB1 with purified or cabbage diets. The beet- and cabbage-containing diets had no effect on the plasma AFP concentration, hepatic tumorigenesis, or the mutagenicity of urine in rats receiving no AFB1. The evidence suggests that non-nutrient components of common vegetables may influence the response to chemical carcinogens, and that AFP determinations are useful in the rapid identification of dietary factors that modify carcinogenesis.

A comparison of the response of woodchucks and rats to variations in dietary lipotrope and lipid content.

A soy protein-based experimental diet for woodchucks (Marmota monax) is described. The diet supported growth of juvenile woodchucks for 12 wk. With this diet, the effects on both woodchucks and rats of increasing dietary corn oil from 5 to 15% and of deleting supplemental lipotropic factors (choline, methionine, folic acid and vitamin B-12) were studied in a 2 X 2 factorial experiment. Both increased lipid and lipotrope deletion resulted in decreased growth in rats, but only increased lipid caused growth depression in woodchucks. Lipotrope depletion resulted in elevated serum markers of hepatic injury and hepatic lipid accumulation in rats but not in woodchucks. Hematological changes induced by the low lipotrope diets included decreased packed cell volume, total hemoglobin and mean corpuscular volume (MCV) in rats but increased MCV in woodchucks. The woodchuck appears to be more resistant than the rat to induction of hepatic injury by lipotrope deficiency.

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.

Toxicologic studies associated with the agricultural use of municipal sewage sludge and health effects among sewage treatment plant workers.

The proposed use of municipal sewage sludges as soil amendments on agricultural land involves potential health risks. Sludges may contain toxic heavy metals, synthetic organics, and pathogens. Studies of animals inhabiting sludge-amended soils, or foraging on crops grown on such soils, have shown an increased deposition of cadmium and polychlorinated biphenyls in animal tissues, hepatic microsomal enzyme induction, altered blood profiles, appearance of mutagens in blood and excreta, and lowered feed intake, feed efficiency, and milk production. Epidemiologic evidence of possible adverse health effects among sewage plant workers exposed to aerosolized pathogens or synthetic organic vapors during wastewater treatment or land spreading of sludge is still inconclusive. Other possible deleterious environmental effects include pollution of groundwater and toxicity to birds consuming worms or insects inhabiting sludge-treated soils.

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.

A comparison of the response of woodchucks and rats to variations in dietary lipotrope and protein content.

Juvenile woodchucks and weanling Fisher F344 rats were fed purified diets with or without supplemental lipotropic factors (choline, methionine, folic acid and vitamin B-12). The diets contained 10 or 20% protein. Lower weight gain due to low protein was observed in both species, while lipotrope depletion resulted in lower gain in male rats only. Urinary excretion of formimino-glutamic acid was higher due to low lipotrope in both species, as was relative liver weight. In rats, lipotrope depletion resulted in hepatic fatty metamorphosis at both levels of dietary protein with the low protein diet resulting in more severe lesions. No liver lesions were observed in woodchucks fed low lipotropes at the higher level of dietary protein, but fatty metamorphosis was observed in those fed the lower protein diets. The lesion was more severe in the low lipotrope group. The woodchuck appears to be less sensitive than the rat to induction of fatty liver by lipotrope deficiency, although the lesion was induced by lowering dietary protein.

Quercetin: a mutagen, not a carcinogen, in Fischer rats.

Purified quercetin, as well as diets containing quercetin at 0.1% and 0.2%, are mutagens to Salmonella typhimurium TA100. This mutagenicity is enhanced with the S9 metabolic activation system. The urine of Fischer rats fed the 0.2% quercetin diet also is mutagenic with the S9 activation system, but the feces of these animals exhibited enhanced mutagenicity only without activation. This may indicate different quercetin metabolites in urine and feces. Rats fed these diets for 64 wk showed no consistent tissue lesions, carcinogenicity, or reproductive changes. Male rats fed 0.2% quercetin showed lowered blood serum glutamic oxaloacetic transaminase and urea nitrogen levels, but these values do not reflect pathological changes.