Metabolism, covalent binding, and mutagenicity of aflatoxin b1 by liver extracts from rats of various ages1, 2

Andrew Jayaraj, James P. Hardwick, Thomas W. Diller, Arlan G. Richardson

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16 Scopus citations

Abstract

The ability of S-9 fractions isolated from the livers of 4-, 12-, and 26-month-old male inbred F344 rats to activate and metabolize the hepatocarcinogen aflatoxin B1 [(AFB1) CAS: 1162-65-8] was studied. The following observations were made: 1) The activation of APB1 to compounds that are mutagenic in the Ames Salmonella-microsome test and to compounds that covalently bind DNA in vitro was similar for liver S-9 from 4- and 12-month-old rats. A 3050% decrease in the activation of AFB1 occurred in rats between 12 and 26 months of age. 2) The in vitro metabolism of AFB1 to chloroform-soluble and water-soluble metabolites was similar for 4- and 12-month-old rats and decreased significantly in rats after 12 months of age. 3) The proportion of most of the chloroform-soluble metabolites of AFB1 formed by liver S-9 from 4-, 12-, and 26-month-old rats was similar. However, the proportion of aflatoxicol (CAS: 29611-03-8) produced by liver S-9 increased approximately twofold in rats between 12 and 26 months of age. 4) The cytochrome P450 content and the NADPH cytochrome c reductase activity of liver microsomes decreased 4045% in rats between 12 and 26 months of age. However, the activities of UDPglucuronyltransferases and most forms of glutathione S-transferase did not change significantly with increasing age in liyer microsomes and cytosol, respectively.

Original languageEnglish (US)
Pages (from-to)95-103
Number of pages9
JournalJournal of the National Cancer Institute
Volume74
Issue number1
DOIs
StatePublished - Jan 1 1985

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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