GSTM1 null polymorphism at the glutathione S-transferase M1 locus: phenotype and genotype studies in patients with primary biliary cirrhosis.

Studies were carried out to test the hypothesis that the GSTM1 null phenotype at the mu (mu) class glutathione S-transferase 1 locus is associated with an increased predisposition to primary biliary cirrhosis. Starch gel electrophoresis was used to compare the prevalence of GSTM1 null phenotype 0 in patients with end stage primary biliary cirrhosis and a group of controls without evidence of liver disease. The prevalence of GSTM1 null phenotype in the primary biliary cirrhosis and control groups was similar; 39% and 45% respectively. In the primary biliary cirrhosis group all subjects were of the common GSTM1 0, GSTM1 A, GSTM1 B or GSTM1 A, B phenotypes while in the controls, one subject showed an isoform with an anodal mobility compatible with it being a product of the putative GSTM1*3 allele. As the GSTM1 phenotype might be changed by the disease process, the polymerase chain reaction was used to amplify the exon 4-exon 5 region of GSTM1 and show that in 13 control subjects and 11 patients with primary biliary cirrhosis, GSTM1 positive and negative genotypes were associated with corresponding GSTM1 expressing and non-expressing phenotypes respectively. The control subject with GSTM1 3 phenotype showed a positive genotype.

Preliminary study to assay plasma amethocaine concentrations after topical application of a new local anaesthetic cream containing amethocaine.

Plasma concentrations of amethocaine were measured after topical application of amethocaine cream 2 g (5% w/w) to the dorsum of the right hand of 10 adult volunteers. The cream was applied for 240 min and plasma was assayed for amethocaine and its metabolite p-n-butylaminobenzoic acid at 0, 30, 60, 90, 120 and 240 min in all 10 volunteers, and at 360 min in seven volunteers, by high pressure liquid chromatography. No amethocaine was detected in the plasma of seven volunteers. Plasma concentrations of amethocaine up to 0.20 mg litre-1 were observed in three volunteers. No significant side effects were seen and pain scores on insertion of a 16-gauge cannula were 0 in all subjects. We conclude that the absence of clinical toxicity in the 10 healthy volunteers was a reflection of slow absorption and tissue hydrolysis of amethocaine after topical dermal application.

The human glutathione S-transferases: a case-control study of the incidence of the GST1 0 phenotype in patients with adenocarcinoma.

The suggestion that individuals with the GST1 0 phenotype have a greater susceptibility to carcinogens than those with other GST1 phenotypes has been examined by using a starch gel zymogram approach to compare the frequency of this phenotype in control subjects and a group of patients with adenocarcinoma of stomach and colon. A significantly greater proportion of the patients with adenocarcinoma demonstrated the null phenotype, odds ratio analysis indicating that individuals with this polymorphic variant have an approximately 3-fold greater risk of developing these cancers.

Alpha, mu and pi glutathione S-transferases: species (Talpa europaea) differences in their expression.

1. Tissue cytosols from Talpa europaea were examined for their glutathione S-transferase isoenzyme content by chromatofocusing, inhibition and immunological techniques and the results compared with data from adult human tissue cytosols. 2. Two sets of glutathione S-transferase isoenzymes were found in liver cytosol of Talpa europaea, they demonstrated similar properties to human alpha and mu isoforms. 3. There was no evidence of expression of the pi isoenzyme set in any of the tissues studied and in this respect Talpa europaea differs from other mammalian species studied so far.