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

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.

Sequential study in rats of nasal and hepatic lesions induced by N-nitrosodimethylamine and N-nitrosopyrrolidine.

Female Sprague-Dawley rats were given an ip dose of N-nitrosodimethylamine (NDMA) and N-nitrosopyrrolidine (NPYR), singly or in combination, and the sequential development of lesions in the liver and nasal cavity was characterized. Liver and nasal tissues were collected from rats given either NDMA or NPYR and killed at 6 or 12 hr and 1, 3, 10, or 30 days. After combination exposure, rats were killed at 3 or 30 days. Olfactory epithelium and adjacent Bowman's glands were specifically targeted by each chemical. Lesions were seen as early as 6 hr and were most severe by 3 days. At the high doses (60 mg/kg NDMA or 100 mg/kg NPYR) regeneration was not complete by 30 days. Hepatic necrosis was seen at 1 and 3 days with NDMA but was not seen with NPYR. Combination exposure appeared to cause additive effects in both the liver and the nasal cavity. Results indicate that a single ip administration of NDMA or NPYR can induce severe and prolonged toxic effects on nasal tissues in rats.

Marek's disease virus (MDV) antigens in the feather follicle epithelium: difference between oncogenic and nononcogenic MDV.

Feather tips from chickens infected with oncogenic or nononcogenic Marek's disease virus (MDV) were individually tested for MDV antigens by the agar-gel-precipitin test to compare antigen contents of feather follicles infected with oncogenic or nononcogenic MDV. There was a significant difference between oncogenic and nononcogenic MDV in the development of MDV antigens in the feather follicle epithelium of infected chickens. Significantly more feather tips from chickens infected with oncogenic MDV were positive for MDV antigens, particularly at 3 and 6 weeks postinoculation, whereas the feather tips from those infected with nononcogenic MDV were rarely positive, whether tested with the homologous or heterologous anti-MDV serum. Such a difference was consistent in separate trials employing three different strains of chickens. Infectious cell-free MDV was extracted more frequently from the feather tips of chickens infected with oncogenic MDV than from those of birds infected with nononcogenic MDV, and the virus titers of extracted MDV were always numerically or statistically higher in birds infected with oncogenic MDV.