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Organ-specific distribution of genotoxic effects in mice exposed to cooked food mutagens
S Knasmüller1, H Kienzl, W Huber
1Institut für Tumorbiologie und Krebsforschung der Universität Wien, Austria.
Abstract:
The induction of organ-specific genotoxic effects of five cooked food mutagens in Swiss albino mice was investigated in microbial animal-mediated assays. The indicator of the induction of DNA damage was a pair of Escherichia coli K12 strains, differing vastly in repair capacity (uvrB/recA versus uvr+/rec+). All compounds gave positive results in the tested dose range between 2.5 and 40 mg/kg body weight (i.p. administration, exposure time 120 min). 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) were slightly more genotoxic than 2-amino-3,8-dimethylimidazo[4,5-f]quinoline (MeIQx), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) which caused similar effects. When the compounds were administered orally, higher doses were required to induce repairable DNA damage. The pattern of organ-specific effects was essentially similar for all compounds; genotoxicity was most pronounced in livers and lungs, whereas in kidneys, spleen and testes comparatively lower effects were measured. The activity of PhIP, MeIQ and IQ in the blood was similar to that observed in the liver. The results obtained in vivo were compared with data gained in vitro with subcellular organ fractions. Our findings indicate the following. (i) The concentrations required to induce repairable DNA damage in microbial animal-mediated assays are substantially higher than might be expected on the basis of the liquid suspension tests. (ii) The ranking order of the genotoxicity of the various compounds in vitro is similar to that measured in vivo, but the differences in genotoxic potencies are less pronounced in the living animal.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Five cooked food mutagens induced DNA damage in mice, with genotoxicity most prominent in livers and lungs. Higher doses were needed for oral administration compared to injections.
Area of Science:
- Toxicology
- Genetics
- Food Science
Background:
- Cooked food mutagens are heterocyclic amines formed during cooking.
- These compounds are suspected carcinogens with potential genotoxic effects.
Purpose of the Study:
- To investigate the organ-specific genotoxic effects of five cooked food mutagens in Swiss albino mice.
- To compare in vivo genotoxicity with in vitro data.
Main Methods:
- Microbial animal-mediated assays using Escherichia coli K12 strains with different DNA repair capacities.
- Intraperitoneal and oral administration of mutagens to Swiss albino mice.
- Comparison of results with in vitro tests using subcellular organ fractions.
Main Results:
- All five tested mutagens (MeIQ, IQ, MeIQx, Trp-P-2, PhIP) induced DNA damage in mice.
- Genotoxicity was highest in livers and lungs, lower in kidneys, spleen, and testes.
- In vivo genotoxicity required higher doses than in vitro tests, with less pronounced potency differences.
Conclusions:
- Cooked food mutagens exhibit organ-specific genotoxic effects in vivo.
- In vivo genotoxicity assays provide a more comprehensive understanding of mutagenic potential compared to in vitro methods.
- Findings highlight the importance of considering in vivo data for risk assessment of food mutagens.