The effect of antilymphocytic and normal horse serum on growth of precancerous foci and development of tumours induced by diethylnitrosamine in rat liver

Abstract

Rats received either a single subcarcinogenic dose of 10 mg of diethylnitrosamine (DENA)/kg 24 hr after two-thirds hepatectomy followed by 2 ml of horse anti-rat antilymphocytic serum (ALS) once weekly for 6 weeks (procedure A), or a carcinogenic regimen of 8 mg DENA/kg day together with 2 ml ALS once weekly for 6 weeks (procedure B). The number and size of the precancerous foci (ATPase-deficient islands) induced in the livers by procedures A and B were measured after fixed periods of time and found not to differ statistically from those occurring in the respective controls consisting of rats receiving normal pre-immune horse serum (HS) or no serum at all. Sera used were not toxic for rat liver. When rats treated according to procedure A were subjected after another 3 weeks to a daily dose of 2·4 mg DENA/kg until death from liver tummours resulted, no effect of the prior ALS treatment on the death rate, as compared with the non-ALS controls, was obtained. However, when rats subjected to procedure B were further left untreated, the rate of death from liver tumours in the ALS group was significantly enhanced as compared with the two control groups. The interpretation of this result was severely hampered because of the non-equivalence, both quantitatively and qualitatively, of the tumours in the ALS, HS and non-serum groups. The sera presumably contained a factor that furthered tumour development other than by immune suppression. However, if it is assumed that the effect of ALS on the neoplastic process was also mediated by immune suppression, then the esults indicated that cells participating in the process of liver carcinogenesis became immunogenic to the cellular immune system beyond the precancerous stage of the ATPasedeficient island cell proper.