Circadian reduction of chromium in the gastric environment.

Samples of gastric juice from variously treated subjects efficiently reduced hexavalent chromium and decreased its mutagenicity. Chromium reduction was due to thermostable components of gastric secretions and was favoured by the acidity of the intragastric environment. The circadian monitoring of pH and of chromium reduction, as assessed by colorimetric analysis at hourly intervals, showed a basal activity (less than 10 micrograms/ml gastric juice) during the night and interdigestive periods, and peaks (tens of micrograms/ml) during the 3-4-h periods after each meal.

Influence of dietary deficiency of nicotinamide on lead toxicity in young rats.

The influence of dietary nicotinamide deficiency on lead intoxication in young developing rats was investigated. The Pb induced an increase in brain dopamine and noradrenaline, inhibition in blood δ-aminolevulinic acid dehydratase activity, an elevation in urinary excretion of δ-aminolevulinic acid and blood and tissue uptake of Pb were significantly more marked in animals maintained on a nicotinamide-deficient diet than those fed a nicotinamide-sufficient diet. The nicotinamide deficiency may enhance the susceptibility to Pb intoxication possible by enhancing the absorption of Pb and altering nicotinic acid metabolism.

Effect of combined exposure to cadmium and ethanol on regional brain biogenic amine levels in the rat.

The effect of ethanol ingestion on regional brain biogenic amine levels in cadmium exposed animals was examined. The rats were given either ethanol (1 g/kg, first week, 5 g/kg, second week and 10 g/kg for rest of the weeks) or cadmium (40 ppm in drinking water) or a combination of both for 8 weeks. Simultaneous exposure to cadmium and ethanol produced a greater elevation of norepinephrine in hypothalamus and mid brain when compared with rats receiving only cadmium.

Influence oe calcium disodium edetate on the toxic effects of lead administration in pregnant rats.

Adverse effects of lead on mothers and foetal development along with lead distribution and their alteration by calcium disodium ethylenediamine tetraacetate (CaNa2EDTA) were investigated in pregnant rats. The number of fetal resorption and abnormal fetuses increased and the number of live fetuses per dam and fetal weight decreased along with increase in liver, kidney, blood, brain and fetus lead levels by lead administration. The treatment with CaNa2EDTA significantly reduced these effects of lead.

Persistence of vanadium compounds in lungs after intratracheal instillation in rats.

Translocation and tissue distribution of two different forms of vanadium compounds, orthovanadate (soluble) and vanadium pentoxide (less soluble), were investigated. Groups of randomly selected rats were injected intratracheally with radiolabeled vanadium (48V) compounds and the animals were sacrificed at 1, 7 and 28 days after treatment. Blood, lungs and other major organs and tissues, namely liver, kidney, spleen, heart, testes, brain, muscle, and bone were sampled and the vanadium contents determined by gamma spectrometry.

Pulmonary metabolism of mutagens and its relationship with lung cancer and smoking habits.

The S-12 fractions of lung peripheral parenchyma obtained from 80 male individuals, aged 17-71 years, were assayed as blind samples for the ability either to convert promutagens into bacterial mutagens or to decrease the potency of direct-acting mutagens in the Ames reversion test. In this system, lung preparations were completely ineffective in activating an N-nitroso compound (i.e.

Metabolism of mutagens and carcinogens in woodchuck liver and its relationship with hepatitis virus infection.

Thirty-six wild-caught woodchucks (Marmota monax) were characterized according to sex, weight, trapping locality, liver pathology, and serum or hepatic markers of woodchuck hepatitis virus. Liver subcellular fractions were assayed for microsomal cytochromes P-450, aryl hydrocarbon hydroxylase, glutathione, cytosolic enzymes involved in its metabolism (glutathione S-transferase, glutathione peroxidase, and glutathione reductase), in the hexose monophosphate shunt (glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase), NADH- and NADPH-dependent diaphorases, and DT diaphorase. Moreover, liver postmitochondrial fractions were assayed for their ability to activate procarcinogens [i.

Effects of aminothiols in 2-acetylaminofluorene-treated rats. II. Glutathione cycle and liver cytosolic activities.

Reduced glutathione, enzymes involved in its metabolism and other cytosolic activities were evaluated in liver preparations of Wistar rats fed with a diet supplemented with 2-acetylaminofluorene (0.05%) and/or with glutathione or N-acetyl-L-cysteine (0.1%).

Effects of aminothiols in 2-acetylaminofluorene-treated rats. III. Metabolic activation of aromatic amines.

Six groups of Wistar rats received a standard diet supplemented with 0.05% 2-acetylaminofluorene and/or 0.1% natural (reduced glutathione) or synthetic (N-acetyl-L-cysteine) aminothiols.

Effects of aminothiols in 2-acetylaminofluorene-treated rats. I. Damage and repair of liver DNA, hyperplastic foci, and Zymbal gland tumors.

One hundred and seventy-nine male Wistar rats were divided into 6 groups and fed with a standard diet supplemented with 0.05% 2-acetylaminofluorene (2AAF) and/or 0.1% glutathione (GSH) or N-acetyl-L-cysteine (NAC).

Circadian monitoring of gastric juice mutagenicity.

The circadian monitoring of intragastric pH and of the mutagenicity of 440 gastric juice samples collected hourly from 22 subjects provided evidence that, irrespective of diagnosis and treatment, a weak yet consistent increase in revertants can be detected in his- Salmonella typhimurium strains during the 3-4-h periods following each meal. The recorded mutagenic activity was not related to the histidine content of gastric juice, was due to thermostable components and was not significantly inhibited by administration of vitamin C. Various genetic mechanisms were involved, which were different from those consequent to the artificial supplementation of gastric juice with sodium nitrite.

Effect of combined exposure to lead and ethanol on some biochemical indices in the rat.

We investigated the effect of daily oral administration to young rats of lead (10 mg/kg) and ethanol (10%, v/v, in drinking water), either alone or in combination, for 8 weeks on the uptake of lead in tissues, brain biogenic amines, hepatic alcohol dehydrogenase and cytosolic and mitochondrial aldehyde dehydrogenase and some selected lead-sensitive variables. Lead given in combination with ethanol produced more pronounced inhibition in the activities of hepatic glutamic oxalacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) as compared to lead alone treatment. Simultaneous exposure to lead and ethanol produced a greater depression of dopamine (DA) and 5-hydroxytryptamine (5-HT) levels in the whole brain of rats, compared to rats treated with lead alone.

Chelation in metal intoxication. XXIV: Influence of various components of vitamin B complex on the therapeutic efficacy of disodium calcium versenate in lead intoxication.

The supplementation of vitamin-B complex reduces lead intoxication. With a view to identify the components of vitamin-B complex responsible for such protection, riboflavin, calcium pentothenate, pyridoxine, nicotinamide, folic acid and cyanocobalamine were investigated for their ability, and their influence on the efficacy of disodium calcium versenate (Na2CaEDTA), to enhance the urinary excretion of lead, mobilize tissue lead and restore lead induced biological alterations in lead intoxicated rats. Folic acid and pyridoxine besides thiamine may be the responsible factors in prophylaxis of lead poisoning by vitamin B complex or in enhancing the antidotal properties of Na2CaEDTA.

Inhibition of urethan-induced lung tumors in mice by dietary N-acetylcysteine.

The thiol N-acetylcysteine (NAC), a precursor of intracellular glutathione (GSH), efficiently prevented the induction of lung tumors in Swiss albino mice, when supplemented to the diet (0.2%) both before and after an i.p.

Detoxifying activities in alveolar macrophages of rats treated with acetylcysteine, diethyl maleate and/or aroclor.

Single or sequential treatment of rats with the thiol N-acetyl-L-cysteine (NAC), the glutathione depletor diethyl maleate (DEM) and the enzyme inducer Aroclor 1254 (AR) produced several significant variations on metabolic activities of pulmonary alveolar macrophages (PAM). Specifically, all three compounds elicited an increase in some oxidoreductase activities, including the two dehydrogenases involved in the hexose monophosphate shunt (G6PD and 6PGD) and NADH- or NADPH-dependent diaphorases. Diaphorase activities were especially increased by sequential treatments with AR and DEM or with DEM and NAC.

Influence of dietary supplementation with thiamine on lead intoxication in rats.

The influence of dietary supplementation with thiamine on lead (Pb) contents in blood and tissues, blood δ-aminolevulinic acid dehydratase (δ-ALAD) activity, and urinary excretion of δ-aminolevulinic acid (δ-ALA) was evaluated in male Sprague-Dawley rats. Groups of randomly selected animals were given a thiamine-deficient diet, a diet containing normal thiamine (20 mg/kg), or a thiamine-supplemented diet (50 mg/kg), along with control drinking water or water containing 100 ppm Pb, for 4 mo. Animals fed the thiamine-supplemented diet (50 mg/kg) and Pb showed decreased urinary excretion of δ-ALA and a decreased inhibition of δ-ALAD activity in blood compared to those given Pb with normal thiamine diet.

Relationships between metabolic deactivation of ICR compounds and their differential mutagenicity in bacteria and cultured mammalian cells.

Preparations of Chinese hamster ovary (CHO) cells decreased the genotoxicity of 3 ICR compounds (ICR 191, ICR 191-OH and ICR 170-OH), while they did not affect the genotoxicity of ICR 170 in the Salmonella reversion test nor in a DNA-repair test in E. coli. These data may contribute towards the explanation of the lack of activity of the two hydroxylated compounds in the CHO/HGPRT forward mutation system, as well as the different rank of mutagenicity of the two chloroethyl compounds in bacteria (ICR 191 greater than ICR 170), compared to cultured mammalian cells and in general to eukaryotic cells (ICR 170 greater than ICR 191).

Chelation in metal intoxication. XXIII: Effect of N-(2-mercaptopropionyl) glycine on lead or lead and ethanol intoxicated rats.

Efficacy of N-(2-mercaptopropionyl) glycine to reduce the body burden of lead and restore the altered biochemical parameters in lead or lead and ethanol intoxicated rats was investigated. The investigation was aimed to suggest suitable prophylaxis of lead poisoning prevalent among workers in lead industry who may also be exposed to ethanol. The rats were given lead (10 mg/kg, p.

Metabolic reduction of chromium by alveolar macrophages and its relationships to cigarette smoke.

Pulmonary alveolar macrophages (PAM), obtained by bronchoalveolar lavage from 47 individuals, reduced hexavalent chromium [Cr(VI)] and decreased its mutagenicity. Their specific activity--mostly mediated by cytosolic, enzyme-catalyzed mechanisms--was significantly higher than in corresponding preparations of mixed-cell populations from human peripheral lung parenchyma or bronchial tree, or from rat lung or liver. At equivalent number of PAM, Cr(VI) reduction, total protein, and some oxidoreductase activities were significantly increased in smokers.

Preventive and therapeutic effects of thiamine, ascorbic acid and their combination in lead intoxication.

Thiamine, ascorbic acid and their combination were investigated for their ability to prevent or treat the experimental lead intoxication in rats. The combination of the two vitamins was most effective in reducing the lead induced inhibition in the activity of blood delta-aminolevulinic acid dehydratase, elevation in the level of blood zinc protoporphyrin and the urinary excretion of delta-aminolevulinic acid and the uptake of lead in blood, liver and kidney. The combined treatment post lead exposure was also most effective in restoring the lead induced biochemical alterations and mobilizing lead from the tissues.

Bacterial genotoxicity of nitrosated famotidine.

Famotidine, a histamine H2-receptor antagonist, was devoid of mutagenic activity in seven his- Salmonella typhimurium strains (TA1535, TA1537, TA1538, TA97, TA98, TA100 and TA102) and was equitoxic in repair-proficient (WP2) and repair-deficient (WP2uvrA, WP67, CM561, CM571, WP100 and CM871) Escherichia coli strains, both in the presence and in the absence of S9 mix containing liver S9 fractions from Aroclor-treated rats. However, after a short pre-incubation step with nitrite in an acidic environment, the drug increased, by a direct mechanism, the number of his+ revertants in Salmonella strains TA100, TA102 and TA97 (a decrease of mutagenicity being conversely observed in TA1535) and of trp+ revertants in E. coli strains WP2uvrA and WP67.

Chelation in metal intoxication XVIII: Combined effects of thiamine and calcium disodium versenate on lead toxicity.

Calcium disodium ethylenediaminetetraacetate (Ca-Na2EDTA; Versenate) was more effective than thiamine (vitamin B1) in enhancing the urinary excretion of lead, reducing tissue lead and restoring lead induced biochemical alterations in rats. However, the combination of CaNa2EDTA and vitamin B1 enhanced the beneficial effect of CaNa2EDTA in lead intoxication and was particularly effective in reducing the brain concentration of lead.