N7-METHYLGUANINE AND O-6-METHYLGUANINE LEVELS IN DNA OF WHITE BLOOD-CELLS FROM CANCER-PATIENTS TREATED WITH DACARBAZINE

Methyl-DNA adducts are induced by a number of lifestyle, environmental and occupational carcinogens, however knowledge about their kinetics is scarce. Here, N7-methylguanine (N7-MeGua) and O-6-methylguanine (O- 6-MeGua) levels were determined in the DNB of white blood cells from e ight cancer patients treated iv with the antitumour drug dacarbazine ( DTIC). Five of the patients were treated with the drug as a single age nt (a single dose of 800 mg m(-2)) and three on three successive days with dacarbazine (225 mg m(-2) day(-1)) in combination with other drug s. The data indicate that maximum adduct levels are reached at 4-8 h a fter treatment and that the amount of N7-MeGua is at least 20-fold hig her than that of O-6-MeGua. The half-life of N7-MeGua is 40-96 h and t hat of O-6-MeGua 25-27 h. Following treatment on three consecutive day s, an accumulation of N7-MeGua was observed but not of O-6-MeGua. The data show substantial interindividual differences in adduct levels but not in the ratio of N7/O-6-MeGua. This may reflect differences in the metabolism of dacarbazine or in repair capacities.