title: DNA base adducts in urine andwhite blood cells of cancer patients receiving combination chemotherapies which include N-methyl-N-nitrosourea.
abstract: Abstract Urinary 3-methyladenine (3-MeAde) excretion andlymphocyte DNA adduct formation was studied in 15 patients receiving methylnitrosourea (MNU) at several dose levels (250 mg, 300 mg and600 mg total dose, 143-385 mg m(-2)) as part of various combination chemotherapies for advanced tumours (malignant melanoma, lymphoblastic lymphosarcorna andHodgkin's disease). Urinary 3-MeAde levels were significantly increased over background in patients at all dose levels (p < 0.001) andthe increases were dose-dependent (r = 0.77, p < 0.01). There were large interindividual variations in the excretion of 3-MeAde at each dose of MNU. In a subset of patients, N7-methyl-2-deoxyguanosine (7-MedG) andO(6)-methyl-2'-deoxyguanosine (O(6)-WedG) levels in DNA from blood leucocytes showed dose-dependent increases, however there were no simple relationships between urinary methylated DNA bases andleucocyte DNA adducts. Levels of adducts in leucocyte DNA (7-MedG, < 17-217 μmol mol(-1) dG; O(6)-WedG, < 1.6-35 μmol mol(-1) dG) were comparable with those reported for other methylating chemotherapeutic drugs. Leucocyte DNA andurinary methyl adducts may be useful markers of individual responses to treatment with methylating drugs.
authors.affiliation: International Agency for Research on Cancer, 150 Cours Albert Thomas, 693727, Lyon, Cedex, 08, France.
authors.forename: V
authors.initials: V
authors.lastname: Prevost
authors.forename: A J
authors.initials: AJ
authors.lastname: Likhachev
authors.forename: N A
authors.initials: NA
authors.lastname: Loktionova
authors.forename: H
authors.initials: H
authors.lastname: Bartsch
authors.forename: C P
authors.initials: CP
authors.lastname: Wild
authors.forename: O I
authors.initials: OI
authors.lastname: Kazanova
authors.forename: A I
authors.initials: AI
authors.lastname: Arkhipov
authors.forename: M L
authors.initials: ML
authors.lastname: Gershanovich
authors.forename: D E
authors.initials: DE
authors.lastname: Shuker