title: Hemoglobin adducts of the human bladder carcinogen o-toluidine after treatment with the local anesthetic prilocaine.
abstract: Prilocaine, a widely used local anesthetic, is metabolized to o-toluidine which is classified as human carcinogen. We aimed to assess the impact of prilocaine-treatment on hemoglobin adducts from o-toluidine. Blood samples were obtained before and 24h after receiving prilocaine local anesthesia (Xylonest, 100mg) from 20 head and neck surgery patients and 6 healthy volunteers. Hemoglobin adducts of o-toluidine and 4-aminobiphenyl were determined by gas chromatography/mass spectrometry. Hemoglobin adducts of o-toluidine were significantly increased 24h after 100mg prilocaine-treatment by 21.6+/-12.8ng/g hemoglobin (mean+/-S.D., N=26; P<0.0001). This corresponds to a 6-360-fold increase of o-toluidine adduct levels in 25 patients from 0.54+/-0.95ng/g before treatment to 22.0+/-13.2ng/g 24h after surgery (mean+/-S.D.). Because of an extremely high background level the increase was only 1.6-fold in one patient (40.9ng/g before and 64.4ng/g 24h after prilocaine injection). Current smoking had no influence on background values and on the increase of o-toluidine adducts. No treatment-related differences were seen in mean hemoglobin adduct levels of 4-aminobiphenyl which were significantly higher in smokers, 0.149+/-0.096ng/g (mean+/-S.D., N=8) as compared to nonsmokers 0.036+/-0.035ng/g (mean+/-S.D., N=16; P<0.01). In conclusion, prilocaine anesthesia leads to a massive increase of hemoglobin adducts of the carcinogenic arylamine o-toluidine. This implies a carcinogenic risk which should be taken into account in preventive hazard minimization.
authors.affiliation: Walther Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians University of Munich, Goethestr 33, D-80336 Munich, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Gaber
authors.forename: Ulrich A
authors.initials: UA
authors.lastname: Harréus
authors.forename: Christoph
authors.initials: C
authors.lastname: Matthias
authors.forename: Norbert H
authors.initials: NH
authors.lastname: Kleinsasser
authors.forename: Elmar
authors.initials: E
authors.lastname: Richter
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000611:Aminobiphenyl Compounds / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D000779:Anesthetics, Local / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use; D002273:Carcinogens / Q000737:chemistry / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006454:Hemoglobins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007279:Injections, Subcutaneous; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015394:Molecular Structure; D011318:Prilocaine / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use; D012907:Smoking; D014052:Toluidines / Q000737:chemistry* / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000097:blood* / Q000601:surgery
chemical_list: D000611:Aminobiphenyl Compounds; D000779:Anesthetics, Local; D002273:Carcinogens; D006454:Hemoglobins; D014052:Toluidines; D011318:Prilocaine; C006757:4-biphenylamine; C023622:2-toluidine