Developmental changes in hepatic activation of dietary mutagens by mice

Chemico-biological Interactions
W E Brennan-CraddockI Rowland

Abstract

Metabolic activation of the food mutagens 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and aflatoxin B1 by female BALB/c mice of different ages (2-24 weeks) was investigated in vivo and in vitro using Salmonella typhimurium TA98 as the indicator organism. The in vivo activation of the three mutagens was investigated in 4- and 24-week-old mice using an intrasanguineous host-mediated assay. All three compounds showed reduced levels of activation with the older hosts. Hepatic S9 fractions from female mice of varying ages between 2 and 24 weeks were used in the in vitro mutagenicity assay. To achieve optimal activation to bacterial mutagens, 5% S9 was required for aflatoxin B1 and Trp-P-2 and 10% S9 for MeIQ; age of donor generally had little effect on the profile of these protein activation curves. Under these optimal conditions MeIQ and Trp-P-2 both exhibited, as before, age-dependent decreases in activation over a wide range of mutagen concentrations, however the in vitro activation of aflatoxin showed no consistent change with age. Spectrophotometric measurements of S9 cytochrome P-450 content showed a decrease in concentration with increasing age, but this was not suffic...Continue Reading

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Citations

Jun 1, 1997·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·F BolognaniI R Rowland
Jul 11, 2002·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Patrick J KleinRoger A Coulombe
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Jan 13, 2018·Toxicology Mechanisms and Methods·He WangXiuying Zhang

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