Development of preneoplastic lesions in the liver and nasal epithelium of rats initiated with N-nitrosodimethylamine or N-nitrosopyrrolidine and promoted with polybrominated biphenyls

Abstract

In rats, N-nitrosodimethylamine (NDMA) and N-nitrosopyrrolidine (NPYR) induce liver tumours and, to a lesser extent, nasal tumours. Polybrominated biphenyls (PBBs) are liver tumour promoters and are highly persistent in tissues of rats. To characterize the development of preneoplastic lesions in the liver and nasal cavity, female Sprague-Dawley rats were initiated with NDMA or NPYR and promoted with Firemaster (FM), a commercial mixture of PBBs. Rats were killed after 30, 120 or 180 days of promotion. Liver and nasal tissues were stained with haematoxylin and eosin and were tested immunohistochemically for glutathione S-transferase placental form (GST-P). Significantly more altered hepatocellular foci (AHF) were evident in rats initiated with NDMA or NPYR and promoted with FM compared with non-promoted groups or rats given only FM. Appreciable numbers of AHF were seen at 120 and 180 days in livers of rats in all other treatment groups, whereas the untreated control rats had no AHF. The percentage volume of the liver occupied by AHF was significantly higher in promoted rats given NDMA than in rats given only NDMA or FM. These results indicate that a single oral dose of PBB can significantly enhance development of AHF in rats initiated with NDMA or NPYR. Preneoplastic lesions in nasal tissues were not detected by staining with GST-P.