Modifying influence of dehydroepiandrosterone or butylated hydroxytoluene treatment on initiation and development stages of azaserine-induced acinar pancreatic preneoplastic lesions in the rat

Abstract

Dietary administration of dehydroepiandrosterone (DHEA) (0.6%) or butylated hydroxytoluene (BHT) (1%) during or subsequent to two i.p. injections of azaserine (30 mg/kg body wt) resulted in significant alteration of yield of preneoplastic lesions in both pancreas and liver. While concomitant application appeared not to have any effect on subsequent development of glutathione S-transferase P form (GST-P) positive hepatocellular lesions in either case, BHT and to a lesser extent also DHEA reduced initiation of pancreatic acinar carcinogenesis. Both BHT and DHEA were associated with significant increase in GST-A form positive pancreatic foci when administered after cessation of carcinogen treatment while clearly inhibiting liver lesion development. The results point to a marked differential in the response of the liver and pancreas to external stimulus with regard to preneoplastic focal lesions while demonstrating significant second stage promotion of pancreatic acinar carcinogenesis by BHT and DHEA.