MODIFYING INFLUENCE OF SWINE SERUM-INDUCED LIVER FIBROSIS ON DEVELOPMENT OF PRENEOPLASTIC LESIONS IN RAT-LIVER

Modifying effects of fibrosis or a cirrhotic state, caused by treatmen t with swine serum (SS), on the induction of preneoplastic focal lesio ns were assessed in a rat medium-term liver bioassay model for the det ection of environmental carcinogens, in which the test compound is adm inistered during the promotion phase after initiation with diethylnitr osamine. In experiment I, repeated intraperitoneal administration of S S concomitantly with the hepatopromoting agent deoxycholic acid (DCA) or phenobarbital (PB) resulted in a cirrhotic state and a significant increase in the number or size of preneoplastic glutathione S-transfer ase placental form (GST-P)-positive liver cell foci as compared to the corresponding DCA or PB alone groups. In experiment II, SS was given prior to commencement of the same medium-term bioassay system, in whic h a known hepatopromoting agent, DCA, 17-alpha-ethynylestradiol, or 2- acetylaminofluorene, was applied. In this case, the liver did not show obvious cirrhotic change and, rather than any enhancement, slight inh ibition of promotion occurred. The results indicate that a coexisting, but not a pre-existing, cirrhotic condition acts to increase growth p ressure on GST-P+ preneoplastic foci, and suggest that concomitant adm inistration of SS with the promoting agent could be applied to improve the sensitivity of the assay protocol.