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Activation of mutagens in cooked ground beef by human-liver microsomes
Abstract:
The total organic base fraction purified from fried ground beef is metabolized by human-liver microsomes to form mutagens detectable by the Ames/Salmonella bacterial assay. The mutagens produced have an absolute requirement for metabolic activation; without it, no increase in the number of revertants over background is seen. Microsomes from human liver activate the mutagens significantly more than microsomes from uninduced mouse or rat liver; the microsomes from one individual were nearly as active as those of Aroclor-induced mice and rats. alpha-Naphthoflavone (ANF) inhibits activation of these mutagenic bases, implying that the metabolism is mediated by the inducible form(s) of cytochrome P-448. Thus, the human liver has the potential to metabolize the cooked beef mutagen(s) to active intermediates, posing a possible mutagenic risk. However, unlike the animal metabolizing system, which needs to be artificially induced, the human system appears to be naturally induced through diet or environmental exposure.
Insights
Fried ground beef contains organic bases that human liver enzymes activate into mutagens. This metabolic activation, potentially influenced by diet, poses a mutagenic risk, unlike in animal models requiring artificial induction.
Area of Science:
- Food toxicology
- Metabolic activation
- Human liver metabolism
Background:
- Fried ground beef contains organic bases.
- These bases can be metabolized into mutagens.
- Metabolic activation is required for mutagenicity.
Purpose of the Study:
- To investigate the mutagenic potential of organic bases from fried ground beef.
- To compare the metabolic activation capacity of human liver microsomes with animal models.
- To identify the metabolic pathway involved in the activation of these mutagens.
Main Methods:
- Purification of the total organic base fraction from fried ground beef.
- Incubation of the fraction with human and animal liver microsomes.
- Detection of mutagens using the Ames/Salmonella bacterial assay.
- Inhibition studies using alpha-naphthoflavone (ANF).
Main Results:
- Human liver microsomes metabolize organic bases from fried beef into mutagens.
- Metabolic activation is essential for mutagenicity.
- Human liver microsomes exhibit higher activation capacity than uninduced animal liver microsomes.
- alpha-Naphthoflavone (ANF) inhibits activation, suggesting cytochrome P-448 involvement.
- Human metabolic system appears naturally induced.
Conclusions:
- The human liver can metabolize cooked beef mutagens into active intermediates, posing a mutagenic risk.
- Human liver's metabolic activation capacity is significant and potentially naturally induced.
- Cytochrome P-448 likely mediates the metabolism of these mutagenic compounds.