Biochemical effects of vinyl chloride monomer on the liver of occupationally exposed workers.

We investigated the effects of vinyl chloride monomer exposure on the liver of 86 workers by measuring beta-glucuronidase, arylsulfatase A, adenosine deaminase, 5'-nucleotidase and routine liver function enzymes in the sera of the workers. In 21 of them, three or more of these parameters were raised, with a significant decrease in the level of blood glutathione and a significant increase in the enzyme activity level of glutathione S-transferase. Of these 21 workers, 14 had fatty liver infiltration, 8 of whom were also suffering from liver enlargement. Also, 4 workers had liver enlargement without fatty infiltration and 3 had enlarged spleens. The study highlights the need for vigilance in environmental monitoring and medical surveillance of workers exposed to this chemical.

Biomonitoring of n-nitroso compounds, nitrite and nitrate in the urine of Egyptian bladder cancer patients with or without Schistosoma haematobium infection.

The excretion of nitrate, nitrite, apparent total N-nitroso compounds and volatile nitrosamines was measured in 24 hr urine from 61 Egyptians, divided into 4 groups: controls, Schistosoma haematobium-infected patients and bladder cancer patients with and without a history of schistosomal infection. Urinary nitrate in S. haematobium-infected patients was significantly higher than in the other 3 groups. Nitrite was below the detection limit of the method (

The effect of dimethylnitrosamine on the activities of renal prenolsulfotransferase and arylsulfatases A and B in Schistosona mansoni infected mice.

The activities of renal phenolsulfotransferase and arylsulfatases A and B were estimated in 400 male Swiss albino mice classified into four groups: Normal controls, Schistosoma mansoni infected group, Dimethylnitrosamine (DMN) treated group and infected treated group. The activity levels of the studied enzymes were significantly increased in all groups when compared with the control group, also the statistical analyses showed a high significant increase of the three enzymes levels in the infected treated group; when compared separately with treated or infected groups. It was concluded, therefore, that schistosomal infection is implicated in the development of kidney cancer which may arise from the pattern of hepatic mixed-function oxidase induction characterized for schistosomiasis and its temporal relationship with the procarcinogenic initiating events. Furthermore, the striking significant increase in the enzymatic activity levels of the acid hydrolases arylsulfatases due to the lesion of both cytotoxic effects of dimethylnitrosamine as well as pathological change of schistosomiasis which may play an active role in the initiation of the malignant process by detoxifying endogenous sulfated aromatic metabolites.

Glutathione S-transferase activity and glutathione content in human bladder carcinoma associated with schistosomiasis: comparison with uninvolved surrounding tissues.

Glutathione (GSH), glutathione S-transferase (GST) activity and GSTpi expression were measured in 10 human bladder tumors and adjacent uninvolved specimens from Egyptian patients with a history of schistosomal infection. GSH was higher in the tumor than in surrounding uninvolved tissue (not significant). Total GST activity per mg tissue protein and GSTpi expression were higher in tumor tissues (P < 0.05) than in uninvolved tissues. There was a positive correlation between GST activity and GSH content and between total GST activity and GSTpi expression in both tumor and uninvolved tissues.

In vivo studies on the effect of some insecticides on the hepatic activities of L-tryptophan 2,3-dioxygenase and pyridoxal phosphokinase of male mice.

The effect of Dimethoate, Carbaryl and Permethrin on the activities of liver L-tryptophan 2,3-dioxygenase (total-, holo-, and apo-forms) and pyridoxal phosphokinase of male mice was investigated. Dimethoate inhibited both enzyme systems after single and repeated dose treatment; except the dioxygenase holo-enzyme after repeated doses. Single dose of Carbaryl treatment inhibited the pyridoxal phosphokinase, total and holo-enzyme of L-tryptophan dioxygenase. However, the repeated dose treatment do not affect both enzyme systems. Permethrin inhibited only total-, holo- and apo-enzymes of L-tryptophan dioxygenase whereas repeated administration has no significant effect on both enzymes. The data indicate that these insecticides may induce abnormal tryptophan metabolism through which some endogenous bladder carcinogens are formed.

Biochemical studies on bilharzial and nonbilharzial hyperoxaluria: effect of pyridoxine and allopurinol treatment.

The urinary excretion levels of oxalic acid, calcium, kynurenic, and xanthurenic acids and serum pyridoxal and pyridoxal phosphate concentrations were determined for nonbilharzial and bilharzial hyperoxaluric patients with or without urinary stones. The effects of pyridoxine and allopurinol treatment were also studied. The different groups studied showed elevated levels of urinary oxalic acid, calcium, kynurenic, and xanthurenic acids as well as decreases in serum pyridoxal and pyridoxal phosphate concentrations. These data indicate that nonbilharzial hyperoxaluric patients suffer from dietary B6 deficiency, whereas bilharzial hyperoxaluric patients may suffer from impaired pyridoxine phosphokinase activity. Pyridoxine supplementation is recommended for the treatment of nonbilharzial hyperoxaluric patients. Allopurinol may be the proper drug in the treatment of oxaluria and stone formation or of bilharzial patients.

Effect of gossypol on liver metabolic enzymes in male rats.

The effects of gossypol on liver metabolism were examined in male rats. Gossypol acetic acid was administered to Sprague-Dawley rats intraperitoneally (i.p.) at 5 mg/kg daily, 5 days/week for 2 weeks. The rats were killed 24 h after the last injection. The liver/body weight ratio (-42%), concentration of liver glutathione (-34%), activities of liver alpha-naphthtylacetate esterase (-30%) and DNase (-39%) were significantly decreased when compared to controls. Hepatic beta-glucuronidase (+37%), RNase (+35%) and serum alkaline RNase (+23%) activities were significantly increased. No changes were found in serum transaminases (SGPT, SGOT) or in hepatic RNA and DNA concentration. Elevation of liver and serum RNase activities suggest that gossypol treatment produces some catabolic effects. The depletion of hepatic glutathione and the elevation of beta-glucuronidase activity indicate that gossypol is hepatotoxic when given at this dose for 2 weeks.

Hepatic microsomal enzymes in Schistosoma mansoni-infected mice: I. Effect of duration of infection and lindane administration on dimethylnitrosamine demethylases.

The prevalence of schistosomiasis in Egypt, its suspected relationship to carcinoma of the bladder, and the inevitable exposure of schistosomal patients to insecticides prompted the undertaking of this study. Dimethylnitrosamine (DMN) demethylases, responsible for the activation of DMN, were assessed in the hepatic microsomes from albino mice under the influence of Schistosoma mansoni infection and/or lindane administration. DMN-demethylase I responded to infection by an early increase in activity, reaching a peak 30 days after disease induction and declining sharply afterwards. DMN-demethylase II followed the same general pattern, but it reached its peak 20 days after infection and declined at a slower rate than DMN-demethylase I. The effects of lindane, an organochlorine insecticide, were also studied on these two enzymes in uninfected mice and in S. mansoni-infected animals after different durations of disease induction. Given orally, in a dose of 40 mg/kg/day for 3 consecutive days, lindane increased the activity of both enzymes. Since DMN requires metabolic activation for its hepatotoxic and carcinogenic actions, alterations in its activating enzymes, as a consequence to schistosomiasis and/or exposure to lindane, may change susceptibility to its toxic and carcinogenic potentials.

Influence of pretreatment with various insecticides on the N-demethylation of dimethylnitrosamine.

The effects of various classes of insecticides were studied on the N-demethylation of dimethylnitrosamine (DMN) by mouse liver enzymes. Organochlorine insecticides, represented by lindane, DDT, and endrin, increased the activities of DMN demethylase I and II. The latter enzyme was more susceptible to the inducive action of the tested chlorinated insecticides. On the other hand, the synthetic pyrethroids, fenvalerate and flucythrinate, did not alter the activity of either enzyme. While pretreatment with carbaryl, a carbamate derivative, was without effect, moderate elevation in the activity of both demethylases was observed following administration of carbofuran. Dimethoate, representing organophosphorus compounds, was the only insecticide tested to inhibit the N-demethylation of DMN, with more pronounced effect on DMN demethylase I. Since DMN requires metabolic activation for its hepatotoxic and carcinogenic actions, alterations in the activities of its metabolizing enzymes as a sequela of exposure to certain insecticides may change susceptibility to its toxicity and/or carcinogenicity.

Steroidal derivatives. Part 4: Synthesis and in vitro anabolic and catabolic properties of a new group of steroidal alkylating agents.

A new group of steroidal alkylating agents has been synthesized for potential anticancer activity. The compounds contain a sulfonic ester, a mono- or a bifunctional nitrogen mustard function attached to an ethyl chain and forming ether linkages at the 3- or 17 beta-position of the steroids selected. The products were tested for their in vitro anabolic and catabolic properties by measuring their effects on the bovine pancreatic ribonuclease.

Effect of some xenobiotics on kynurenine hydrolase and kynurenine aminotransferase of mouse liver.

The effects of some xenobiotics on the activity of the B6-dependent kynurenine hydrolase (KH) and kynurenine aminotransferase (KATE) in mouse liver, were investigated. Polychlorinated biphenyl (Aroclor 1254) (400mg/kg/day x4) markedly decreased the activity of both enzymes. Benzo(a)pyrene (BP) and 3-methylcholanthrene (3-MC) (40mg/Kg/day x1) as well as phenobarbital (PB) (75mg/kg/day x3) did not alter the activity of KH, while that of KATE was mildy reduced. The response of the two enzymes to treatment with chlorpromazine (CPZ) (5mg/Kg/day x5) were opposite with marked elevation of KH and inhibition of KATE activities. Treatment with B-naphthoflavone (B-NF) (80mg/Kg/day x2), Pyrazole (200mg/Kg/day x1) or indole (400mg/kg/day x1) produce no change in the activity of either enzyme. It, seems therefore, that Aroclor (1254) and chlorpromazine may cause disordered kynurenine metabolism through alterations in the activities of its metabolizing enzymes. This, in turn, might affect nicotinamide adenine dinucleotide biosynthesis and/or the accumulation of some tryptophan metabolites suspected of being carcinogenic or co-carcinogenic.

Urinary alpha-naphthyl acetate esterases: a preliminary screening test for bladder cancer.

The urinary activities of alpha-naphthyl acetate esterases were measured for groups of bilharzial and nonbilharzial patients with benign urologic diseases and for others with bladder cancer. All these patients showed elevation in the urinary enzyme activity over that given by healthy controls. Bilharzial and nonbilharzial bladder cancer patients exhibited significant increase in urinary enzyme activity as compared with corresponding groups with benign urologic diseases A level of 50 units of enzyme activity was taken as a limit to discriminate between bladder cancer patients and those patients with benign urologic diseases. The specificity and sensitivity of this urinary test exceeded 90% with low falsely positive and negative results. The data of the present study recommended the use of urinary alpha-naphthyl acetate esterases activity as a preliminary screening test for bilharzial and nonbilharzial bladder cancer patients.

Biochemical and cytochemical changes of alpha-esterases activity in long-term oral contraceptive users.

PIP: The alpha-esterases activity was measured in the serum and vaginal fluid of 39 women who used (OCs) oral contraceptives for long periods of time (12-15 years). The results were compared with the activity of 30 control fertile females who did not take any OCs. The alpha-esterases activity was measured by cytochemical and modified simple reproducible biochemical methods. The biochemical study revealed that serum alpha-esterases activity is not affected either by long-term use of OCs or by different types of cervical infections. On the other hand, the cytochemical and biochemical results show that there is a significant increase in the activity of vaginal alpha-esterases in pill users accompanied with cervicitis. The increase in vaginal alpha-esterases activity may shed light on the possible relationship between the activity of alpha-esterases and malignancy.^ieng

The activities of urinary alpha-esterases in bilharziasis and their possible role in the diagnosis of bilharzial bladder cancer in Egypt.

The activities of serum and urinary alpha-esterases were studied in 49 bilharzial bladder cancer patients, 92 bilharzial patients with other, different, urologic diseases and 22 normal healthy controls. Among the group studied, the bilharzial bladder cancer patients showed the highest level of urinary-alpha-esterases and the lowest ratio of serum/urine activity. These patients showed a significant increase in the activity of urinary alpha-esterases as compared with the normal controls or with the other different bilharzial groups. Although a small but significant increase in serum activity was observed in all the bilharzial groups studied compared with the normal healthy controls, no significant difference was found between the bilharzial bladder cancer patients and the other different bilharzial groups. Biochemical determination of urinary alpha-esterases for bilharzial patients revealed a high degree of accuracy for the diagnosis of bilharzial bladder cancer (95.9%), with low falsely positive (3.26%) and falsely negative (4.08%) results. The activity of urinary alpha-esterases in recommended as a screening test for bilharzial bladder cancer.