Metabolism, Covalent Binding, and Mutagenicity of Aflatoxin B1 by Liver Extracts From Rats of Various Ages
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 i...
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Veröffentlicht in: | JNCI : Journal of the National Cancer Institute 1985-01, Vol.74 (1), p.95-103 |
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Sprache: | eng |
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Zusammenfassung: | 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 30–50% 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 40–45% 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. |
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ISSN: | 0027-8874 1460-2105 |
DOI: | 10.1093/jnci/74.1.95 |