Teresa Wrońska-Nofer

DNA damage induced by nitrous oxide: study in medical personnel of operating rooms.

Occupational exposure to anaesthetics such as nitrous oxide (N(2)O) and halogenated hydrocarbons has been suggested to increase risk of genetic damage. However, the dose-dependency of genotoxic effects has not been unequivocally established and their relation to occupational exposure limit (OEL) remain obscure. In this study, the genotoxicity associated with occupational exposure to anaesthetics has been investigated in a group of 55 female nurses and 29 male anaesthesiologists active for at least 5 years in a working environment containing variable concentrations of N(2)O and halogenated hydrocarbons. 83 unexposed health care workers (52 female nurses and 31 male doctors) matched for age, gender, smoking habit and employment duration were included in the control group. Genotoxicity has been assessed using comet test. Concentrations of nitrous oxide, sevoflurane and isoflurane monitored by gas chromatography and mass spectrometry made possible to relate the extent of DNA damage to the level of exposure. Our results for the first time document a positive correlation between the DNA damage and the N(2)O levels in the ambient air. By contrast, no correlation has been observed between genotoxic effects and concentrations of sevoflurane and isoflurane. The extent of genetic injury was especially aggravated among nurses and anaesthesiologists exposed to N(2)O in concentrations exceeding OEL (180 mg/m(3)). We conclude that occupational exposure to N(2)O is associated with increased DNA damage and that the level of exposure plays a critical role in this regard.

Structural aspects of experimental carbon disulfide neuropathy: I. Development of neurohistological changes in chronically intoxicated rats

SummaryIn white rats exposed to CS2 vapors (at the average concentration of 1.5 mg per liter of air) over 1 to 15 months, the progressive development of structural lesions was studied in the selected areas of the central and peripheral nervous system. Gradual destruction of myelinated fibers within the white matter of spinal cord and in the peripheral nerves was observed. Morphological alterations of the body of the nerve cells were also encountered, but their pathologic nature and their relation to the exposure were disputable even at the stage of advanced CS2 induced myelo- and neuropathy.

The effect of combined exposures to ethanol and xylene on rat hepatic microsomal monooxygenase activities

Studies on rats treated for 8 months with ethanol (10% solution in drinking water) and simultaneously exposed to xylene vapour (12,000 mg/m3, 5 hr daily) for the last 9 days revealed that the chemicals exert additive stimulatory effect on hepatic microsomal monooxygenase: the activity of aniline p-hydroxylase increased by 380%, microsomal ethanol oxidizing system by 92%, NADPH-cyt. c reductase by 30% and the level of cytochrome P-450 by 70%. The changes were accompanied by a marked proliferation of smooth endoplasmic reticulum (a subcellular site of cytochrome P-450 monooxygenases in the hepatocytes) and an increased NADPH-Fe2+- and ascorbate-Fe2+-driven lipid peroxidation in microsomal membranes--a potential toxic mechanism. Interaction of ethanol and xylene with cytochrome P-450 monooxygenases may enhance metabolic capacity of the liver and in consequence modify biological/toxic effects of occupational exposure to solvents in the case of alcohol abuse.

The effect of carbon disulphide and atherogenic diet on the development of atherosclerotic changes in rabbits

Abstract The influence of chronic CS 2 intoxication on lipid spectrum in the aorta and blood and on the grade of atheromatosis of the aorta and coronary vessels was studied in rabbits with experimentally induced prolonged hyperlipemia. Rabbits fed on standard laboratory chow served as controls. The following biochemical and morphological alterations due to the atherogenic diet alone and those due to hyperlipemia with parallel CS 2 exposure were demonstrated respectively: (a) in blood — an approximate 4- and 5-fold elevation of the total (both free and esterified) serum cholesterol with a simultaneous rise in phospholipid and triglyceride (atherogenic diet alone) fractions; (b) in the aortic arch — a 40 and 100% increase in total cholesterol with a 5- and 10-fold rise in the level of cholesterol esters and an approximately uniform 100% increase in the triglyceride fraction; (c) gross atheromatosis of the aorta and histological coronary lesions, both markedly enhanced as a result of chronic CS 2 intoxication. Evidence was presented of an enhanced susceptibility of the arterial wall to the atherogenic diet under the influence of chronic CS 2 intoxication with special reference to the individual regional susceptibility of arterial coronary vessels.

Effect of cadmium on arterial blood pressure and lipid metabolism in rats.

A total dose of 8 mg cadmium acetate/kg body weight was administered by repeated i.p. injection to female Wistar rats for 12 weeks. Slight, but significant, increases in blood pressure were recorded. The lipid concentration in serum and other tissues examined was not significantly affected, apart from a decrease in hepatic triglyceride. The blood cadmium (Cd) concentration was increased 10 times and Cd in the aortic wall was 4 times higher in treated rats. Cd affects hepatic lipid metabolism and it is considered that the increase in blood pressure is associated with accumulation of Cd in the arterial walls.

Structural alterations and content of nicotinamide-adenine nucleotides in skeletal muscle of rat in chronic experimental carbon disulfide intoxication

SummaryThe histological nature and extent of muscular lesions and the content of nicotinamide-adenine nucleotides in the skeletal muscles of white rats exposed to CS2 at a concentration of 1.5 mg/l for 1 to 14 months were studied.From the 5th month of exposure muscle atrophy of the denervation type was the constant histological finding. Five months later a significant fall in the nucleotide level was noted, parallel to apparent paresis of the hind limbs and gross muscular atrophy. No evidence of any inflammatory reaction or dystrophic myopathy was found. Reduction of the nucleotide content was attributed therefore to secondary alterations in the metabolism of skeletal muscle undergoing atrophy.

Increased oxidative stress in subjects exposed to carbon disulfide (CS2) – an occupational coronary risk factor

Abstract. There is considerable epidemiological evidence that workers exposed to carbon disulfide (CS2) develop premature atherosclerosis leading to increased rates of coronary heart disease (CHD), but mechanisms underlying this association remain obscure. The present study documents that occupational exposure to CS2 modifies the oxidative status of plasma, which is a major determinant of the susceptibility to atherosclerosis. Concentrations of thiobarbituric reactive substances (TBARS), which reflect lipid peroxidation processes in plasma, were determined in 29 men who were exposed to CS2 for more than 20 years, in 24 patients with peripheral atherosclerosis, and in 30 unexposed, healthy control subjects. TBARS concentrations were significantly increased both in CS2-exposed subjects and in patients with peripheral atherosclerosis. Subjects in both groups presented also with decreased levels of plasma α-tocopherol, a major plasma antioxidant. In addition, decreased activities of two enzymatic antioxidants, glutathion peroxidase and catalase, were noted both in CS2-exposed subjects and patients with peripheral atherosclerosis. Finally, LDL isolated from both groups showed increased susceptibility to transition metal-induced oxidation in vitro. It is concluded, that occupational exposure to CS2 produces oxidative stress in plasma. This may favor the development of atherosclerosis and increase the incidence of CHD in workers exposed to CS2.

Genotoxicity of industrial dyes under the inductive effect of ethanol on monooxygenase system in mice

The genotoxic effects of triarylmethane (Acid Green 16, C.I.44025) and arylmonoazo (Basic Orange 28, developed by Boruta Pigment Plant, Poland, C.I. undisclosed) dyes, were evaluated in Balb/C mice. Animals were fed for 6 days nutritionally adequate Portagen liquid diet (1 kcal/ml) or isocaloric alcoholic diet containing 5% (w/v) ethanol (36% of total calories) in order to induce the cytochrome P-4502E1 monooxygenase. Dye compounds were administered intraperitoneally 30 h before the test at doses: 90 mg/kg of Acid Green 16 and 70 mg/kg of Basic Orange 28. Bone marrow micronucleus test was used for evaluation of genotoxicity of the dyes. Ethanol caused an increase of the level of cytochrome P-450 by 200% and activities of 7-ethoxycoumarin O-deethylase (ECOD) by 650%, 7-ethoxyresorufin O-deethylase (EROD) by 460% and glutathione (GSH)-S-transferase by 60% in the liver. Both dyes exerted genotoxic effect as inferred from a 3-fold increase of frequency of micronucleated polychromatic erythrocytes in bone marrow, and a further increase (2-fold) was caused by ethanol liquid diet combined with Acid Green 16 treatment. Basic Orange 28 genotoxicity remained unaffected by ethanol. It is concluded that: (1) enhancement of genotoxic effect of Acid Green 16 by ethanol is caused by induction of cytochrome P-4502E1 monooxygenases resulting in an increased bioactivation of the dye; (2) lack of enhancement of the genotoxic effect of Basic Orange 28 by ethanol probably results from the dye- and ethanol-mediated stimulation of GSH-S-transferase, bypassing the cytochrome P-4502E1 bioactivation step.

Effect of alcohol intake on some disturbances induced by chronic exposure to carbon disulphide in rats, II. Biochemical and ultrastructural alterations in the peripheral nerves

The effect of chronic ethanol (EtOH) administration on CS2-induced peripheral neuropathy in rats was studied. Rats were exposed to 0.8 mg/l CS2 for 12-15 months and to 10% EtOH as only drink during the last 4 months of the experiment. Some biochemical correlates of Wallerian degeneration of the peripheral nerve were estimated and ultrastructural examinations of the peripheral nerves were performed. It was shown that EtOH augmented the alterations in lipid content provoked by CS2 in the peripheral nerves, i.e. an increase in cholesterol esters and in the ratio of cholesterol esters to free cholesterol (E/F ratio) and a decrease in phospholipid content. The magnitude of ultrastructural changes induced by CS2 in the nerves was increased by EtOH.

Effect of alcohol intake on some disturbances induced by chronic exposure to carbon disulphide in rats I. Behavioural alterations

Female white Wistar rats were exposed to CS2 vapour (0.8 mg CS2/1 air) 11 months and to 10% ethanol as the only drinking liquid for the last 3 months of exposure. Spontaneous exploratory motor activity (SEMA), open-field behaviour, passive avoidance performance and the avoidance acquisition were tested. Ethanol did not change the exploratory motor activity and behaviour of CS2-exposed rats in the open-field and passive avoidance tests but it affected their performance in the conditioned avoidance test. The analysis of data suggests that ethanol may adversely affect memory and learning ability in CS2-exposed rats.