Genotoxic analysis of four lipid-peroxidation products in the mouse lymphoma assay.

Lipid-peroxidation products are formed by the thermal treatment of foodstuffs, as well as by endogenous processes. In addition, they are also common environmental pollutants originating from many different sources. Since conflicting data exist on their possible risk for humans, we have selected four lipid-peroxidation products namely acrolein, crotonaldehyde, 4-hydroxy-hexenal (4-HHE) and 4-oxo-2-nonenal (4-ONE) to determine their ability to induce mutagenicity in mammalian cells. There is an important lack of mutagenicity data on mammalian cells for such products, which presents an important gap for any risk-assessment estimation. We have used the mouse lymphoma assay (MLA) to determine the mutagenic potential of these four compounds. This assay detects a broad spectrum of mutational events, from point mutations to chromosome alterations. The results obtained indicate that the four selected compounds are mutagenic in the MLA assay, showing a direct dose-effect relationship. The relative mutagenic potencies according to the induced mutant frequency (IMF) are as follows: crotonaldehyde (IMF=758.5×10(-6)), 4-ONE (IMF=700.5×10(-6)), acrolein (IMF=660.5×10(-6)) and 4-HHE (IMF=572×10(-6)). Although the differences between the induced mutant frequencies for these compounds are not very large, the α,β-unsaturated aldehyde 4-oxo-2-nonenal turned out to be the agent most mutagenic. This is because its induced mutant frequency was reached after treatment with 10μM, while 50μM of the other compounds was needed to reach the reported frequencies.