Syncarcinogenic effects on the initiation of rat liver tumors by trans-4-acetylaminostilbene and 2-acetylaminofluorene

Abstract

Two carcinogenic aromatic amines with different organotropism were tested for syncarcinogenic effects in rat liver in an initiation-promotion experiment. Trans-4-acetylaminostilbene (AAS) and 2-acetylaminofluorene (AAF) were administered as initiators in four doses each either alone or sequentially combined in both orders. The promotion phase was started by partial hepatectomy and continued by adding phenobarbital (250 p.p.m.) to the drinking water for 26 weeks. The number/cm2 of tissue section and average size of hyperplastic foci, glucose-6-phosphatase-deficient and gamma-glutamyl-transpeptidase-positive foci were determined and a total area of lesions calculated during the promotion phase after 18 and 31 weeks, and in the post-promotion phase after 42 and 47 weeks. The synergistic effects of AAS and AAF were clearly more than additive if compared with the sum of the effects exerted by each compound individually. The sequence in which both initiators were administered remarkably influenced the development of lesions. They developed more rapidly and persisted longer in the post-promotion phase when AAS was administered first and AAF second. In the final stage, enzyme altered foci increased in the livers of both combination groups, but to a greater extent in the AAS-AAF group. It is concluded that the two arylamides damage DNA independently. In addition, however, the results suggest that AAS acts predominantly as an initiator, and AAF as a weak initiator and a strong promoter in what is considered the initiation phase of this experiment.