POTENTIAL EFFECT OF SODIUM-NITRITE ON THE EXPRESSION OF NUCLEAR PROTOONCOGENES DURING 2-ACETYL AMINOFLUORENE-INDUCED HEPATOCARCINOGENESIS IN RATS

2-acetyl aminofluorene (AAF) reacts in acidic conditions with nitrous fume yielding N-nitroso-AAF (N-NO-AAF), as previously described, that exerts more toxic and mutagenic effects than its parental compound. In this study, the effect of sodium nitrite (NaNO2) on the tumorigenicit y of AAF in rats fed with AAF and NaNO2 was observed. Wistar rats were divided into five groups: group I served as control; group II were tr eated with NaNO, (0.3%); group III was given 0.02% AAF alone; groups I V and V received both AAF and NaNO2 (0.2 and 0.3% respectively) in the ir diet for 12 weeks. At the end of the experiment, all rats in groups III, IV and V developed early stage phenomena of hepatocellular carci noma, including hepatomegaly with variable-sized foci and neoplastic n odules. Severe damage was observed in the rats treated with AAF and Na NO,. Feeding of AAF (0.02%) for 3 months elevated the levels of c-Fos, c-Jun and c-Myc proteins in the rat livers. The AAF-induced c-Jun, c- Fos and c-Myc expressions were significantly magnified (P < 0.001) by NaNO,. These data confirmed that the strengthening of AAF-induced hepa tocarcinogenesis by NaNO2 should be associated with its enhancing effe ct on the AAF-induced increases in the expressions of c-Jun, c-Fos and c-Myc. (C) 1997 Elsevier Science Ireland Ltd.