NITRO MUSKS ARE COGENOTOXICANTS BY INDUCING TOXIFYING ENZYMES IN THE RAT

In the present study, musk xylene (MX) and musk ketone (MK) were exami ned for their potency to induce toxifying enzymes in the liver of Spra que-Dawley rats, using an in vivo/in vitro model. After i.p. applicati on of 10, 20 and 40 mg/day MX and MK over a period of 5 days, 9000 x g liver fractions (S9(M)) were used to study the toxification of a numb er of well-known pregenotoxicants in the SOS chromotest, i.e., benzo[a ]pyrene (B[a]P), 2-aminoanthracene (2-AA), and aflatoxin B-1 (AFB(1)). The genotoxic potencies of B[a]P, 2-AA and AFB(1) in the presence of S9(M) were compared to those obtained in the presence of S9 fractions of untreated animals (S9(0), negative control). S9(M) fractions derive d from MK-treated rats showed an increased potency to toxify B[a]P, 2- AA and AFB(1) in comparison to S9(M) fractions (for instance: TIP[toxi fying induction potency] = 70 per nmol AFB(1) using 10 mg MK treatment ). In comparison, S9(M) fractions from MX-pretreated rats exhibited an increased genotoxicity only when using 2-AA (TIP = 0.04) and AFB(1) ( TIP = 61) as pregenotoxicants, but not when using B[a]P. To summarize the results, both NM and MK were strong inducers of toxifying liver en zymes. Therefore, these compounds seem to be cogenotoxicants for a num ber of well-known pregenotoxicants. Synergistic effects were found whe n using inducers of toxifying enzymes and pregenotoxicants in the in v ivo/in vitro induction model.