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Musk ketone enhances benzo(a)pyrene induced mutagenicity in human derived Hep G2 cells
V Mersch-Sundermann1, H Schneider, C Freywald
1Department of Toxicology and Ecotoxicology, FB VI, University of Trier, 54286 Trier, Germany. mersch@rumms.uni-mannheim.de
Abstract:
Musk ketone is a widely used artificial fragrance which has been identified in human fatty tissue and milk. The mutagenic and comutagenic effects of this compound were studied in micronucleus tests with a human derived hepatoma cell line (Hep G2). Exposure of the cells to MK alone in the range between 5 and 5000 ng/ml did not cause induction of MN. When the cells were treated simultaneously with MK (5-5000 ng/ml) and 0.2 microg/ml benzo(a)pyrene, no synergistic effects were detected; benzo(a)pyrene (B(a)P) itself caused an 1.5-fold increase of MN over the spontaneous background frequency (60 versus 39 MN/1000 binucleated cells). In a third experimental series, the cells were pretreated with MK for 28h and subsequently exposed to 0.2 microg/ml B(a)P. In this case, a pronounced comutagenic effect was observed: The LOAEL for MK was 0.05 microg/ml. With higher doses (0.5, 1.0 and 5.0 microg MK/ml), a significant increase of B(a)P induced MN frequencies was measured, the induction rates being 50, 66, and 88%, respectively. Additional measurements of 7-ethoxyresorufin deethylase indicated that MK induces cytochrome P450 isoenzymes (1A1) which play a key role in the activation of B(a)P. The results of the present study show that MK amplifies the genotoxic effects of B(a)P in human derived cells and indicate that exposure of humans to MK might increase their susceptibility to the health hazards of B(a)P and other polycyclic aromatic hydrocarbons.
Insights
Musk ketone (MK) amplifies the genotoxic effects of benzo(a)pyrene (B(a)P) in human cells. Exposure to MK may increase susceptibility to B(a)P and similar compounds, highlighting potential health risks.
Area of Science:
- Toxicology
- Genetics
- Environmental Health
Background:
- Musk ketone (MK) is a synthetic fragrance found in human tissues.
- Potential genotoxic and comutagenic effects of MK require investigation.
- Benzo(a)pyrene (B(a)P) is a known genotoxic polycyclic aromatic hydrocarbon.
Purpose of the Study:
- To evaluate the mutagenic and comutagenic potential of Musk ketone (MK).
- To assess the interaction between MK and benzo(a)pyrene (B(a)P) in human-derived cells.
- To investigate the role of MK in the metabolic activation of B(a)P.
Main Methods:
- Micronucleus (MN) tests were conducted using Hep G2 cells.
- Cells were exposed to MK alone, simultaneously with B(a)P, or pretreated with MK before B(a)P exposure.
- Cytochrome P450 1A1 (CYP1A1) activity was measured using 7-ethoxyresorufin deethylase assay.
Main Results:
- MK alone did not induce micronuclei (MN).
- Pretreatment with MK significantly increased B(a)P-induced MN frequencies, demonstrating a comutagenic effect.
- MK induced CYP1A1, enhancing B(a)P activation.
Conclusions:
- Musk ketone exhibits comutagenic activity by amplifying B(a)P's genotoxicity in human cells.
- MK-induced CYP1A1 is implicated in the enhanced genotoxic effects of B(a)P.
- Human exposure to MK may increase susceptibility to the health risks associated with B(a)P and other PAHs.