No abstract

Fast transport kinetics of 51Cr (VI) into red blood cells (RBCs) in vitro were studied. No significant species differences were found between RBCs of man and rat. The uptake of 51Cr (VI) by RBCs in whole blood was composed of two different first order processes of different velocities (apparent t 1/2 of 22.7 s and 10.4 min for man and 6.9 s and 10.1 min for rat, respectively). However, even after longer time periods a fixed portion of approximately 15% of the administered dose remained in the plasma and did not penetrate into RBCs Over the entire concentration range studied (10 microM-50 mM), the fast initial uptake followed Michaelis-Menten kinetics. The maximal capacity of this Cr(VI) transport into RBCs of man and rat was 3.1 X 10(8) CrO4(2-) ions X cell-1 X min-1 and 2.5 X 10(8) CrO4(-2) ions X cell-1 X min-1, respectively. It is likely that Cr(VI) is transported into RBCs via a physiological anion carrier ("band-3-protein").

The interaction of chromium(III) and chromium(VI) with the phosphate groups of di- and triphosphate nucleotides were examined by 31P-NMR spectroscopy. Chemical shifts of the phosphate groups, indicating the formation of Cr-nucleotide complexes, could only be detected with Cr(III). When Cr(III) was generated from Cr(VI) by reduction with an excess of glutathione, nearly the same chemical shifts could be observed. This indicates that glutathione is not capable of trapping Cr(VI) by reduction with subsequent formation of stable Cr-GSH complexes, thus preventing the binding of chromium to important target molecules as DNA or nucleotides. Using radioactively-labelled chromium no 51Cr(VI) bound to any nucleic acid, whereas 51Cr(III) bound in increasing order to poly(A).poly(U), calf thymus DNA and poly(G).poly(C). Furthermore, the melting temperature of nucleic acids increased in the same order only in the presence of Cr(III). Possible genotoxic consequences in vivo of the presented data in vitro concerning the binding of Cr(III) to sensitive molecular targets are discussed in detail.

No abstract

Male Wistar rats were subacutely treated with sublethal doses of HgCl2, CdCl2, Pb(NO3)2, or Na-aurothiomalate. The metal preparations contained trace doses of radioactive nuclide. Based on the doses given and on the radioactivity excretion in urine and faeces the body burden was determined. After the metal treatment periods, some of the animals received N-acetylcysteine (up to 100 mg/kg daily, on 6 consecutive days, i.p.), and the effect of this potential chelator on metal excretion was monitored. The excretion of Hg (after dosing with HgCl2) was not influenced by N-acetylcysteine. The elimination of Cd in urine (after dosing with CdCl2) was increased by a factor of four. Also, the elimination of Pb [after dosing with Pb(NO3)2] was gradually increased (in faeces and urine) by increasing doses of N-acetylcysteine. After dosing with Na-aurothiomalate, the excretion of Au in urine was increased to about 30%. The data suggest some activity of N-acetylcysteine in facilitating excretion of Pb, Cd or Au, but not of Hg.