Rats bearmg the fast-growmg AH-l 30 Yoslnda ascItes hepatoma showed a marked cachectlc response which has been previously reported [Tessltore et al (1987) Blochem J 241, 153-1591 Thus tumour-bearmg ammals showed slgmficant decreases m body and muscle weight (soleus and gastrocnemms) as compared to both pair-fed and ad hbltum-fed animals These decreases were related to an enhanced proteolytlc rate m the muscles of the tumour-bearmg ammals as measured by the tyrosme released m m vitro assays In an attempt to elucidate which proteolytlc system IS directly responsible for the decrease m muscle mass, we have studied both lysosomal and non-lysosomal (ATP-dependent) proteolytlc systems m this animal model While the enzymatic activities of the mam cathepsm (B and B + L.) systems were actually decreased m gastrocnemms muscles of tumourbearmg rats, thus mdicatmg that lysosomal proteolysls was not involved, the ublqmtm pools (both free and conjugated) were markedly altered as a result of tumour burden These were associated with an increased ublqmtm gene expression m muscle of tumour-beanng rats, over 500% m relation to non-twnour bearers, thus suggesting that the ATP-dependent proteolytlc system may be responsible for the muscle proteolysls and wastage observed m this animal tumour model The fact that we have previously shown that TNF enhances the ublqultmlzation of muscle proteins FEBS Lett 323, 21 l-2141, together with the high clrculatmg levels of TNF detected m rats bearmg the Yoshlda hepatoma allows us to suggest that the cytokme may be responsible, most probably mdlrectly, for the activation of the referred proteolytlc system m tumour-bearing rats