Journal article
Evidence of two separate mechanisms for the decrease in aryl sulfotransferase activity in rat liver during early stages of 2-acetylaminofluorene-induced hepatocarcinogenesis
Molecular carcinogenesis, Vol.9(1), pp.2-9
01/1994
DOI: 10.1002/mc.2940090103
PMID: 8297481
Abstract
Enzymatic and immunohistochemical experiments were conducted to evaluate the mechanistic basis for the downregulation of the important detoxication/bioactivation enzyme aryl sulfotransferase IV (AST IV) during 2‐ acetylaminofluorene (2AAF)–induced hepatocarcinogenesis. To distinguish between possible genotoxic and cytotoxic actions of 2AAF, three different dietary protocols were used in these experiments: group 1 received 2AAF for 12 wk, group 2 received 2AAF for 3 or 6 wk and then a control diet lacking xenobiotics for 3 or 6 wk, and group 3 received 2AAF for 3 or 6 wk and then phenobarbital for 3 or 6 wk. When hepatic AST IV activity was assessed, N‐hydroxy‐2AAF sulfotransferase activity was found to decrease 80–90% in response to 2AAF feeding, but activity recovered to essentially normal levels in the livers of rats subsequently placed on either control diets or diets with phenobarbital, suggesting a reversible cytotoxic mechanism for loss of AST IV activity. However, when liver sections from the rats were evaluated immunohistochemically, two distinct patterns were detected for the downregulation of AST IV expression was observed throughout the liver and among most but not all newly developed nodules. In tissue sections from rats initially fed 2AAF and then placed on a control diet (group 2) or a diet with phenobarbital (group 3), the nodules continued to show low levels of AST IV expression, while expression in the areas surrounding nodules returned to the normal, high levels. In addition, among those rats fed 2AAF for just 3 wk and then control diet or diet containing phenobarbital for 6 wk, only rats fed phenobarbital developed altered foci that stained weakly for AST IV expression. These results show that there were two kinds of 2AAF‐mediated decrease in hepatic AST IV activity: a general overall loss of AST IV expression dependent on administration of 2AAF and reversible upon removal of 2AAF from the diet and a loss of AST IV expression among newly developed liver foci and nodules that persisted in the absence of 2AAF administration and appeared to be a property of 2AAF‐induced subpopulations of cells. These patterns may correspond, respectively, to cytotoxic and genotoxic mechanisms of 2AAF action. © 1994 Wiley‐Liss, Inc. Copyright © 1994 Wiley‐Liss, Inc., A Wiley Company
Details
- Title: Subtitle
- Evidence of two separate mechanisms for the decrease in aryl sulfotransferase activity in rat liver during early stages of 2-acetylaminofluorene-induced hepatocarcinogenesis
- Creators
- David P. Ringer - Oklahoma Medical Research FoundationBoyd A. Howell - Samuel Roberts Noble FoundationTom R. Norton - Samuel Roberts Noble FoundationGary W. Woulfe - Samuel Roberts Noble FoundationMichael W. Duffel - University of IowaStanley D. Kosanke - University of Oklahoma Health Sciences Center
- Resource Type
- Journal article
- Publication Details
- Molecular carcinogenesis, Vol.9(1), pp.2-9
- Publisher
- Wiley Subscription Services, Inc., A Wiley Company
- DOI
- 10.1002/mc.2940090103
- PMID
- 8297481
- ISSN
- 0899-1987
- eISSN
- 1098-2744
- Number of pages
- 8
- Language
- English
- Date published
- 01/1994
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984303162102771
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