Short term induction of preneoplastic nodules in the rat liver. I. The role of 2-AAF as selecting agent

Abstract

Induction of preneoplastic nodules by a single administration of N-nitrosodiethylamine (NDEA) as initiator and selective stimulation of proliferation by 2-acetylaminofluorene ( 2-AAF) in combination with partial hepatectomy was used to study the effect of different doses of NDEA and 2-AAF on number and size of the nodules. There was a positive relationship between the number of preneoplastic nodules and the dose of NDEA. The marked increased capacity to proliferate with increasing amounts of NDEA suggests an acquired genetically fixed phenomenon. Morphologically there was a striking uniformity of the nodules induced by different doses of NDEA during the first 2 weeks of development, and stimulated by different doses of 2-AAF. This suggests that possible subpopulations were not formed at all during the experimental period of 2 weeks. Alternatively, a genetic heterogenicity may be expressed at a later stage or under different conditions. The effect of 2-AAF reached a plateau at 5 mg/kg body weight; higher concentrations did not influence the number and size of the nodules. Although there was a steady increase in size of the nodules during early development, the number of nodules reached a maximum value at 2 days after partial hepatectomy. It is concluded that 2-AAF only permits selective outgrowth of previously initiated cells by its cytotoxic effects on the surrounding normal tissue and that the carcinogenic properties of 2-AAF in this model do not come to expression.