Urinary glucuronidase and arylsulfatases in identical twins of bladder cancer patients.

Studies showing that bladder cancer patients have unusually high levels of urinary beta-glucuronidase and arylsulfatases A and B led to the suggestion that these urinary enzymes may participate in bladder cancer etiology. An alternative explanation of the high levels of these urinary enzymes in bladder cancer patients is that the disease itself causes the elevation. Since the levels of these enzymes are genetically determined, measuring these enzymes in healthy identical twins of bladder cancer patients can test whether high enzyme levels occurred prior to bladder cancer. Five healthy identical cotwins of bladder cancer patients, together with matched controls, were measured for urinary beta-glucuronidase, arylsulfatases A and B, and two other lysosomal enzymes as controls, alpha- and beta-galactosidases. The mean levels of all five enzymes were not very different in the cotwins and controls, suggesting that high levels of urinary enzymes observed in bladder cancer patients are a consequence of disease rather than occurring prior to disease and contributing to its etiology.

Arylhydrocarbon hydroxylase activity and cytochrome P-450 in human tissues.

The stability and distribution of arylhydrocarbon hydroxylase activity in four human tissues has been examined. Two tissues, liver and lung, were obtained from autopsy samples while lymphocytes and placenta were obtained from cell lines and donors. Marked differences in arylhydrocarbon hydroxylase activity were observed between tissues and individuals, with liver being the richest source. Activity in all tissues was stable at 4 degrees C for 24 h, but freeze-thawing markedly reduced hydroxylase activity in liver. Using gel exclusion chromatography, the molecular weight of a non-dissociated form of arylhydrocarbon hydroxylase was estimated to be about 400000. A heme staining band corresponding to a molecular weight of 50000 was observed after polyacrylamide gel electrophoresis of liver microsomal preparations. This appears to be a cytochrome P-450 subunit based on correlations between staining intensity and hydroxylase activity in tissues and partially purified preparations examined.

The Gus-e locus regulates estrogen repression of androgen-induced beta-glucuronidase expression in mouse kidney.

Both enzyme activity and mRNA concentration of beta-glucuronidase were measured in kidneys of mice treated with testosterone and the synthetic estrogen, diethylstilbestrol. Six congenic strains, all having a C57BL6/J genetic background but each having a different haplotype of the beta-glucuronidase gene complex, were compared. In each strain the induction caused by androgen was partially repressed by estrogen. The extent of this antagonism varied among the six haplotypes and was not coordinate with the extent of induction by androgen alone. Antagonism appears to be regulated by at least two alleles of a new locus, Gus-e, within the beta-glucuronidase gene complex. Repression by estrogen, like induction by androgen, appears to take place primarily at the transcriptional level. Kinetic studies revealed that estrogen causes the androgen response curve to plateau earlier and at a lower level. This suggests that estrogen increases the rate of gene deactivation rather than decreasing the rate of gene activation. Isoelectric focusing of beta-glucuronidase from Gus-ea and Gus-eb mice and their F1 progeny revealed that the genes are regulated in cis. Together, these findings support a model in which both sex hormones exert their effects on separate DNA response elements located in close proximity to the gene or within the gene itself.