3.3.9 GST Theta Class
3.3.9.1 Substrates GSTT1-1Dichloromethane, ethylene dibromide, buta-
diene diepoxide, cumene hydroperoxide (moderate-high), 1,2-epoxy-3 (4-
nitrophenoxy-propane, ethylene oxide, methyl bromide, methylene chloride,
4-nitrobenzyl chloride, 4-nitrophenethylbromide, phenethylisothiocyanate.
GSTT2-2Cumene hydroperoxide, menaphthyl sulfate.3.3.9.2 Polymorphisms A null allele for the GSTT1 gene (GSTT1^ 0/^0 )is
also fairly common. In Caucasians, approximately 19.7% (range 13–26%) are
homozygous for the null allele. The null allele is much more common in Asians
(mean 47%, range 35%–52%). In Nigerians, 38% were homozygote null
compared to 24% in African-Americans (Garte et al., 2001).
Several epidemiological studies comparing persons with the GSTT1 null
phenotype (GSTT1^0 ) have been completed. Of the completed studies with at
least 100 cases and 100 controls, three found an association with the null
phenotype and increased risk for cancer, two found a higher rate of the null
phenotype in controls, and found no significant change (Risch et al., 2001).
One study suggested an increased risk for myelodysplastic diseases but another
study failed to find an association. There may be an increased risk for some
types of brain tumors. In a recent Danish study, there was a stronger
association with early-onset lung cancer (OR = 9.6) and null genotype with an
OR = 2.4 overall (Sorensen et al., 2004).
3.3.10 GST Zeta Class
The GST Zeta class was initially identified by a BLAST homology search (Tong
et al., 1998). It appears to play a role in acetoacetate metabolic pathways. Its role
in the metabolism of drugs is not known (Board and Anders 2005).
3.3.10.1 Substrates GSTZ1-1Dichloroacetic acid(conversion to glyoxy-
late) and other haloacetic acids, maleylacetoacetate cis–trans isomerase
(penultimate step in tyrosine degradation), ethacrynic acid (low).
3.3.11 Incubation Conditions and Analytical Methods
For most general purposes, one incubates substrates in the presence of cytosol
and added glutathione. A more purified preparation of the major cytosolic
TABLE 3.15 Frequency of GSTT1 null genotypes in German control and cancer
patients.
Gene
Percentage in German
Caucasians (controls)Lung
cancer (%)Adenocarcinoma
(%)GSTT1 null 18.8 (n = 65) 12.8 (n = 49) 14.7 (n = 22)
GSTT1 non-null 81.2 (n = 281) 87.2 (n = 334) 85.3 (n = 128)
GLUTATHIONE-S-TRANSFERASES 81