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SUMMARY BackgroundHepatotoxicity results in the withdrawal of thiopurines drugs, azathioprine (AZA) and mercaptopurine (MP), in up to 10% of patients with inflammatory bowel disease. Our group previously demonstrated that allopurinol with AZA ⁄ ciclosporin ⁄ steroid 'triple therapy' improved renal graft survival.

Molybdenum isotope variations in mafic arc lavas have mainly been attributed to the influence of slab-derived components, such as subducted sediment melts and aqueous fluids. The latter have been hypothesised to fractionate Mo isotopes through interaction with the oceanic crust and carry an isotopically heavy signal that is transferred to the source of arc magmas. Thus, understanding Mo isotope systematics in subduction zones requires characterising the Mo isotope composition of slab-derived fluids and their influence on the Mo isotope budget of arc magmas. However, Mo isotope data reported to date show a considerable influence from subducted sediments that complicate accurate constraints being placed on the fluid contribution. We present Mo isotope data for mafic lavas from the Izu arc, a highly depleted oceanic island arc whose magma compositions show a dominant control from slab-derived fluids. The lavas from the Izu volcanic front are isotopically heavier than MORB and the depleted mantle. Their d 98/95 Mo (the relative difference in measured 98 Mo/ 95 Mo to NIST 3134) systematically varies with indicators for fluid-mobile element enrichment, suggesting that slab-derived fluids in the Izu arc have heavy Mo isotope compositions. Additionally, co-variations with radiogenic 143 Nd/ 144 Nd and 176 Hf/ 177 Hf point to a relationship between the addition of aqueous fluids and compositional heterogeneity of the sub-arc mantle. We present mass balance models that show that the influence of subduction zone fluids on the trace element pattern of arc magmas is more dominant when these are added to a more depleted and refractory sub-arc mantle, which preferentially melts due to a relatively higher fluid flux. The mass balance of Mo in the Izu arc predicts a light Mo isotope composition for the residual oceanic crust as a result of the preferential removal of isotopically heavy Mo during slab dehydration, consistent with previous suggestions for the Mariana arc and isotopically light Mo previously reported for eclogites.

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