The mutagenicity of tetrachloroethene (tetra) and its S conjugate, S-(1,2,2-trichlorovinyl)glutathione (TCVG) was investigated using a modified Ames preincubation assay. TCVG was a potent mutagen in presence of rat kidney particulate fractions containing high concentrations of gamma-glutamyl transpeptidase (GGT) and dipeptidases. Purified tetra was not mutagenic without exogenous metabolic activation or under conditions favoring oxidative metabolism. Preincubation of tetra with purified rat liver glutathione (GSH) S-transferases in presence of GSH and rat kidney fractions resulted in a time-dependent formation of TCVG as determined by (HPLC) analysis and in an unequivocal mutagenic response in the Ames test. Experiments with tetra in the isolated perfused rat liver demonstrated TCVG formation and its excretion with the bile; bile collected after the addition of tetra to the isolated perfused liver was unequivocally mutagenic in bacteria in the presence of kidney particulate fractions. The mutagenicity was reduced in all cases by the GGT inhibitor serine borate or the beta-lyase inhibitor aminooxyacetic acid. These results support the suggestion that cleavage of the GSH S conjugate formed from tetra by the enzymes of the mercapturic acid pathway and by beta-lyase may be involved in the nephrocarcinogenic effects of this haloalkene in rats.

Zusammenfassung: Wir berichten ª ein fª Jahre altes M~idchen mit einer pl6tzlich aufgetretenen Sehschw~iche. Vorausgegangen war ein leichter Luftwegsinfekt mit Kopfschmerzen und Erbrechen. Die zerebrale Computertomographie (CCT) erbrachte keine auff~illigen Befunde an den Optikusnerven. Die kraniale MRT zeigte ein Optikus-scheiden6dem des linken Nervus opticus (T2-Wichtung) und eine diffuse Signalanhebung beider Nervi optici nach Gd-DTPA-Gabe. Es wurde die Diagnose einer bilateralen anterioren Optikusneuritis gesteltt. Obwohl die bilaterale Optikusneuritis im Kindesalter eine gute Prognose hat, kann die Optikusneuritis das erste Symptom einer multiplen Sklerose sein, die sich erst nach vielen Jahren manifestiert. Schlª Neuritis nervi optici -Optikusneuritis 9 Sehschw~iche -Multiple Sklerose -Kindesalter Bilateral Anterior Opticus Neuritis in a Five-Year-Old GirlAbstraet: We report about a five-year-old girl with sudden visual loss following a mild respiratory infection with headache and vomiting. CT scan showed no abnormal findings in the visual tract. Cranial MRI revealed an edema of the left optic nerve (T2weighted) and diffuse Gd-DTPA enhancement of both optic nerves; therefore a bilateral anterior optic neuritis was diagnosed. Although bilateral optic neuritis has a good prognosis in childhood, ir can be the first symptom of multiple sclerosis, which may develop even many years later.