GLUTATHIONE TRANSFERASE-ACTIVITY AND FORMATION OF MACROMOLECULAR ADDUCTS IN 2 CASES OF ACUTE METHYL-BROMIDE POISONING

Objectives-To determine the activity of glutathione transferase and to measure the S-methylcysteine adducts in blood proteins, after acute i nhalational exposure to methyl bromide. To examine the influence of th e polymorphism of glutathione-S-transferase theta (GSTT1) on the neuro toxicity of methyl bromide. Methods-Two workers acutely exposed to met hyl bromide with inadequate respiratory protective devices were poison ed. Seven weeks after the accident, blood samples were drawn from both patients, for measurement of glutathione transferase activity in eryt hrocytes (conjugator status-that is, GSTT1 phenotype) and measurement of binding products of methyl bromide with blood proteins. Conjugator status was determined by a standard procedure. The binding product of methyl bromide, S-methylcysteine, was measured in globin and albumin. Results-Duration and intensity of exposure were identical for both pat ients as they worked together with the same protective devices and wit h similar physical effort. However, one patient had very severe poison ing, whereas the other only developed mild neurotoxic symptoms. The fi rst patient was a ((conjugator)) with normal glutathione transferase a ctivity, whereas this activity was undetectable in the erythrocytes of the second patient, who consequently had higher concentrations of S-m ethylcysteine adduct in albumin (149 v 91 nmol/g protein) and in globi n (77 v 30 nmol/g protein). Conclusions-Methyl bromide is genotoxic an d neurotoxic. Its genotoxicity seems to be the consequence of the alky lating activity of the parent compound, and conjugation to glutathione has a protective effect. The data presented here suggest a different mechanism for methyl bromide neurotoxicity which could be related to t he transformation of methylglutathione into toxic metabolites such as methanethiol and formaldehyde. If such metabolites are the ultimate to xic species, N-acetylcysteine treatment could have a toxifying rather than a detoxifying effect.