title: Formation of DNA adducts in HL-60 cells treated with the toluene metabolite p-cresol: a potential biomarker for toluene exposure.
abstract: We have examined DNA adduct formation in myeloperoxidase containing HL-60 cells treated with the toluene metabolite p-cresol. Treatment of HL-60 cells with the combination of p-cresol and H(2)O(2) produced four DNA adducts 1: (75.0%), 2: (9.1%), 3: (7.0%) and 4: (8.8%) and adduct levels ranging from 0.3 to 33.6 x 10(-7). The levels of DNA adducts formed by p-cresol were dependent on concentrations of p-cresol, H(2)O(2) and treatment time. In vitro incubation of p-cresol with myeloperoxidase and H(2)O(2) produced three DNA adducts 1: (40.5%), 2: (28.4%) and 3: (29.7%) with a relative adduct level of 0.7x10(-7). The quinone methide derivative of p-cresol (PCQM) was prepared by Ag(I)O oxidation. Reaction of calf thymus DNA with PCQM produced four adducts 1: (18.5%), 2: (36.4%), 3: (29.0%) and 5: (16.0%) with a relative adduct level 1.6x10(-7). Rechromatography analyses indicates that DNA adducts 1-3 formed in HL-60 cells treated with p-cresol and after myeloperoxidase activation of p-cresol were similar to those formed by reaction of DNA with PCQM. This observation suggests that p-cresol is activated to a quinone methide intermediate in each of these activation systems. Taken together, these results suggest PCQM is the reactive intermediate leading to the formation of DNA adducts in HL-60 cells treated with p-cresol. Furthermore, the DNA adducts formed by PCQM may provide a biomarker to assess occupational exposure to toluene.
authors.affiliation: Department of Neurological Surgery, Brain Tumor Research Center, Box 0555, University of California-San Francisco, San Francisco, CA 94143-0555, USA.
authors.forename: Nilesh W
authors.initials: NW
authors.lastname: Gaikwad
authors.forename: William J
authors.initials: WJ
authors.lastname: Bodell
mesh_terms: D000818:Animals; D002417:Cattle; D003408:Cresols / Q000378:metabolism* / Q000494:pharmacology* / Q000633:toxicity; D018736:DNA Adducts / Q000032:analysis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004784:Environmental Monitoring / Q000379:methods; D018922:HL-60 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015394:Molecular Structure; D009195:Peroxidase / Q000378:metabolism; D013997:Time Factors; D014050:Toluene / Q000378:metabolism* / Q000633:toxicity
chemical_list: D003408:Cresols; D018736:DNA Adducts; C032538:4-cresol; D014050:Toluene; D006861:Hydrogen Peroxide; D009195:Peroxidase