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We study primary and secondary reactions induced by 600 MeV proton beams in monolithic cylindrical targets made of natural tungsten and uranium by using Monte Carlo simulations with the Geant4 toolkit [1–3]. Bertini intranuclear cascade model, Binary cascade model and IntraNuclear Cascade Liège (INCL) with ABLA model [4] were used as calculational options to describe nuclear reactions. Fission cross sections, neutron multiplicity and mass distributions of fragments for 238U fission induced by 25.6 and 62.9 MeV protons are calculated and compared to recent experimental data [5]. Time distributions of neutron leakage from the targets and heat depositions are calculated.