title: Nitro musks are cogenotoxicants by inducing toxifying enzymes in the rat.
abstract: In the present study, musk xylene (MX) and musk ketone (MK) were examined for their potency to induce toxifying enzymes in the liver of Sprague-Dawley rats, using an in vivo/in vitro model. After i.p. application of 10, 20 and 40 mg/day MX and MK over a period of 5 days, 9000 x g liver fractions (S9M) were used to study the toxification of a number of well-known pregenotoxicants in the SOS chromotest, i.e., benzo[a]pyrene (B[a]P), 2-aminoanthracene (2-AA), and aflatoxin B1 (AFB1). The genotoxic potencies of B[a]P, 2-AA and AFB1 in the presence of S9M were compared to those obtained in the presence of S9 fractions of untreated animals (S9O, negative control). S9M fractions derived from MK-treated rats showed an increased potency to toxify B[a]P, 2-AA and AFB1 in comparison to S9O fractions (for instance: TIP[toxifying induction potency] = 70 per nmol AFB1 using 10 mg MK treatment). In comparison, S9M fractions from MX-pretreated rats exhibited an increased genotoxicity only when using 2-AA (TIP = 0.04) and AFB1 (TIP = 61) as pregenotoxicants, but not when using B[a]P. To summarize the results, both MX and MK were strong inducers of toxifying liver enzymes. Therefore, these compounds seem to be cogenotoxicants for a number of well-known pregenotoxicants. Synergistic effects were found when using inducers of toxifying enzymes and pregenotoxicants in the in vivo/in vitro induction model.
authors.affiliation: Department of Medical Microbiology and Hygiene, Faculty of Clinical Medicine Mannheim, Ruprecht-Karls-University of Heidelberg, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Mersch-Sundermann
authors.forename: M
authors.initials: M
authors.lastname: Emig
authors.forename: A
authors.initials: A
authors.lastname: Reinhardt
mesh_terms: D000818:Animals; D004790:Enzyme Induction; D004926:Escherichia coli / Q000235:genetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013014:SOS Response, Genetics; D014992:Xylenes / Q000494:pharmacology*
chemical_list: D014992:Xylenes; C031447:musk xylene; C031448:musk ketone