Intermediate-level radioactive waste (ILW) includes cellulosic materials, which under the hyperalkaline conditions expected in a cementitious geological disposal facility (GDF), will undergo abiotic hydrolysis forming a variety of soluble organic species. Isosaccharinic acid (ISA) is a notable hydrolysis product, being a strong metal complexant that may enhance the transport of radionuclides to the biosphere. This study shows that irradiation with 1 MGy of -radiation under hyperalkaline conditions enhances the rate of ISA production from alkali hydrolysis of cellulose, indicating that radionuclide mobilisation to the biosphere may occur faster than previously anticipated. However, irradiation also made the cellulose fibres more available for microbial degradation and fermentation of the degradation products, producing acidity that inhibited ISA production via alkali hydrolysis. The production of hydrogen gas as a fermentation product was noted, and this was associated with a substantial increase in the relative abundance of hydrogen-oxidising bacteria. Taken together these results expand our conceptual understanding of the mechanisms involved in ISA production, accumulation and biodegradation in a biogeochemically active cementitious GDF.