DNA-BASE ADDUCTS IN URINE AND WHITE BLOOD-CELLS OF CANCER-PATIENTS RECEIVING COMBINATION CHEMOTHERAPIES WHICH INCLUDE N-METHYL-N-NITROSOUREA

Urinary 3-methyladenine (3-MeAde) excretion and lymphocyte DNA adduct formation was studied in 15 patients receiving methylnitrosourea (MNU) at several dose levels (250 mg, 300 mg and 600 mg total dose, 143-385 mg m(-2)) as part of various combination chemotherapies for advanced tumours (malignant melanoma, lymphoblastic lymphosarcoma and Hodgkin's disease). Urinary 3-MeAde revels were significantly increased over ba ckground in patients at all dose levels (p < 0.001) and the increases were dose-dependent (r = 0.77, p < 0.01). There were large interindivi dual variations in the excretion of 3-MeAde at each dose of MNU. In a subset of patients, N7-methyl-2'-deoxyguanosine (7-MedG) and O-6-methy l-2'-deoxyguanosine (O-6-MedG) levels in DNA from blood leucocytes sho wed dose-dependent increases, however there were no simple relationshi ps between urinary methylated DNA bases and leucocyte DNA adducts. Lev els of adducts in leucocyte DIVA (7-MedG, < 17-217 mu mol mol(-1) dG; O-6-MedG, < 1.6-35 mu mol mol(-1) dG) were comparable with those repor ted for other methylating chemotherapeutic drugs. Leucocyte DNA and ur inary methyl adducts may be useful markers of individual responses to treatment with methylating drugs.