Musk ketone enhances benzo(a)pyrene induced mutagenicity in human derived Hep G2 cells

Musk ketone is a widely used artificial fragrance which has been identified in human fatty tissue and milk. The mutagenic and comutagenic effects of t his compound were studied in micronucleus tests with a human derived hepato ma cell line (Hep G2). Exposure of the cells to MK alone in the range betwe en 5 and 5000 ng/ml did not cause induction of MN. When the cells were trea ted simultaneously with MK (5-5000 ng/ml) and 0.2 mug/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 vers us 39 MN/1000 binucleated cells). In a third experimental series, the cells were pretreated with MK for 28 h and subsequently exposed to 0.2 mug/ml B( a)P. In this case, a pronounced comutagenic effect was observed: The LOAEL for MK was 0.05 mug/ml. With higher doses (0.5, 1.0 and 5.0 mug MK/ml), a s ignificant increase of B(a)P induced MN frequencies was measured, the induc tion rates being 50, 66, and 88%, respectively. Additional measurements of 7-ethoxyresorufin deethylase indicated that MK induces cytochrome P450 isoe nzymes (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 inc rease their susceptibility to the health hazards of B(a)P and other polycyc lic aromatic hydrocarbons. (C) 2001 Elsevier Science B.V. All rights reserv ed.