Diverse expression profiles of glutathione-S-transferase subunits in mammalian urinary bladders

The hGSTM1 null genotype has been associated with increased susceptibility to urinary bladder cancer. However, the extent to which the GSTM1 subunit actually contributes to GST activities in mammalian urinary bladders is not clear. For adult mice, urinary bladders exhibited GST activity which was among the highest observed in the tissues tested. The mouse bladder GST activity with the 1-chloro 2,4-dinitrobenzene substrate was also more than 10-fold greater than that of rat and human bladders. A large increase in mouse bladder GST activity occurs during early development with the sharpest increase between 7 and 17 days of age. Subunit compositions of GSTs in adult mouse, human, and rat bladders are also markedly different. The mGSTM1 subunit is by far the predominant GST in mouse bladder, with increases in mGSTM1 between 7 and 17 days accounting for the sharp rise in GST activity during maturation. By contrast, Pi class GSTs predominate in both human and rat bladders. Investigators seeking to establish direct connections between susceptibility to bladder cancer and the hGSTM1 gene deletion should take into account the fact that the hGSTM1 subunit, even when present, represents a very minor fraction of the GST protein in human bladder.