ELSEVIER Chemico-Biological Interactions 92 (1994) 343-350 Ch~,,-ak,k,~¢,~ Molecular mechanisms for the regulation of aryl sulfotransferase IV expression during 2-acetylaminofluorene-induced hepatocarcinogenesis in rat • a~ David P. Ringer , Tokunbo Yerokun b, Akbar S. Khan a aBiomedical Division, S.R. Noble Foundation, Inc., Ardmore, OK, USA bDepartment of Biology, University of Arkansas at Pine Bluff, Pine Bluff, AR, USA Received I September 1993; revision received 24 November 1993; accepted 14 December 1993 Abstract The dietary administration of 2-acetylaminofluorene to male rats to induce hepatocarcino- genesis causes a reversible as well as persistent down-modulation of N-hydroxy-2AAF sulfotransferase activity. Studies are presented which indicate that several molecular mechanisms may be involved in the down-regulation of sulfotransferase activity and expres- sion. These include carcinogen-mediated inactivation of sulfotransferase mRNA or protein, interference with hormonal regulation of sulfotransferase expression, and, mutation of the sulfotransferase gene. Keywords: Altered sulfotransferase expression; Chemical carcinogenesis; Aryl sulfotrans- ferase IV; Hormonal regulation; Rat liver In an effort to identify and investigate critical events which may lead irreversibly to tumor formation, this laboratory has employed an experimental model of car- cinogenesis. Teebor and Becker [1] reported that during the cyclic dietary adminis- tration of the hepatocarcinogen, 2-acetylaminofluorene (2AAF), where one cycle was defined as 3 weeks on diet containing 0.06% 2AAF followed by 1 week on diet * Corresponding author, Carcinogenesis Group, Noble Center for Biomedical Research, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA. 0009-2797/94/$07.00 © 1994 Elsevier Science Ireland Ltd. All rights reserved SSDI 0009-2797(94)0331 I-U