A.R. Volpe ‘, k?Navarra. F!Preziosi. ’ Dept. of Chemistry.Catholic Univefsi& Rome, ha/y; Dept. of Pha~acology. C&olic Universilv.Rome. Ita& We have prevfousfy shown that the toxicity of the anticancer drug hydroxyurea(HU) is strongly increased in adrenalectomized (ADX) rats. In this studv we investigated if nitric oxide (NO) may play a role in increased HU toxicity in ADX rats. Intact or ADX rats were treated with graded doses of HU. and the NO content in plasma (estimated as L-citrulline, the stable co-product of NO synthase) was assessed 2 h later. TABLE1 L-Citnhe.
means f SEM (n = 51 inid
2% !pM/ml plasma)
Vehicle HU lOmgrk9
11.24f0.69 12.33 l 0.32
HU 30mg/kg HU 100mgkg
18.95* 0.9s 30.44l 1.51
HlJ 300 m&a
HU 800 m&k;
81.92 f 0.95 178.18 f 1.10
ADX rats (nbikni p:asmr! 4599*010 47.90 f 0.42
P +zO.Oi
P < 0.01
52.93f 0.34
P < 0.01
P c 0.01 P z 0.01 P < 0.01
Go.??* a.57 72.46 f 0.60 90.48 f 0.50
P 4 0.01 P < 0.01 P < 0.01
These findings show that HU dose-dependently increases NO total-body synthesis in intact and ADX rats. Interestingly. adrenalectomy itself dramatically increases NO production, indicating that adrenal corticosteroids might down-regulate not only inducible. but also constitutive NO synthase. Supported bv MURSI. 40% 1993n4.
Visual Evoked Potentials In Workers Chronically Exposed to Low Level Concentrations of Toluene A. Vrca. V KaraEiC.0. BofiEeviC, D. Prpic-Majic. Institute for Medical Research and Occupational H&&h, Zagreb The investigation was conducted in two groups of subjects. comparable by age, eduction and years of work. The first group consisted of 49 workers in a printing-press, all of whom used toluene as an organic solvent over the last 30 years. During this period technology did not change very much. Working conditions, ventilation, and the kind and number of working places remained almost the same. The average work service in the workers was 21.4 years. The second group consisted of 59 workers who had never been in contact with any known neurotoxic substance. The level of exposure in both groups was assessed by detection of the concentration of toluene in peripheral blood and of hippuric acid in urine in randomly chosen subjects. All analysis were performed on Wednesday morning before workers entered the workrooms. Hippuric acid was analyzed the same day after the work shift. The results of all measurements show statistically higher values in the exposed workers. The concentration of toluene in exposed workers was 0.036 mg7l. while in non-exposed workers it was only 0.00096 mg/l. In all subjects we recorded visual evoked potentials using stimulation by structural stimuli check-board of reversal type. The responses were recorded on the primary visual cortex by Oz electrode. N75, PlG3 and N145 waves showed significantly higher amplitudes, and PlOO wave significantly higher latency in the exposed group. Key words: neurotoxicity; organic solvent; toluene; VEP
Biochemical Renal Changes in Workers Exposed to Soluble Nickel Compounds A. Vvskocil. C. Viau. V Senft. J. Kohout. M. Cizkova. Dkp. mkdecine do travail et hygi&ne du milieu. Universiti de Montrka4 Canada; Clinic of Occupational Medicine, Universily Hospital. Pizen, Czech Repub!ic: Dept. of Hygiana, Medical Faculty. Charles UniversiM Hradec Ki#ov&, Czech Republic Biochemical markers of kidney damage were examined in 14 male and 12 female workers highly exposed to soluble nickel compounds in a chemical plant. The results were compared to those obtained in 12 male and 12 female matched controls. The concentration of nickel in urine of male and female workers averaged 5.0 and 10.3 fig g-l creatinine. respectively. The mean duration of exposure in male and female workers was 25 and 15 years. No difference was found in the mean urinary excretion of lactate dehydrogenase, albumin and transferrin in both sexes, total proteins. &-microglobulin (@2-m)and retinal-binding protein (RBP) in males and lysozyme in females. Lysozyme and N-acetyf-8-D-glucosaminidase (NAG) were increased in male and total proteins, &m, NAG and RBP in female exposed workers. Significant correlations between urinary concentrations of nickel on one side and that of &ni in women (r = 0.462, P = 0.022) and men (r = 0.41, P = 0.018) and of NAG in men (r = 0.405, P = 0.019) on the other side were found in exposed subjects. Results indicate adverse effects of soluble nickel compounds on the kidney tubuiar function. In agreement with literature data it seems that those effects occur only at high exposure levels.