DETECTION OF DNA METHYLATION ADDUCTS IN HODGKINS-DISEASE PATIENTS TREATED WITH PROCARBAZINE

The aim of the present study was to assess the relationship between do se of the methylating agent procarbazine (PCZ), DNA methylation adduct formation and response to chemotherapy treatment in 23 Hodgkin's dise ase patients receiving MOPP/ABV combination therapy. The DNA adducts, 7-methyldeoxyguanosine (7-medG) and O-6-methyldeoxyguanosine (O-6-medG ), were measured in leucocytes at the end of the first cycle of PCZ tr eatment (77-100 mg m(-2) per day). 7-medG was detected in only two pat ients prior to treatment and O-6-medG was below the detection limit (0 .08 mu mole per mole dG) in air subjects prior to treatment. The mean levels after PCZ treatment were 12.55 mu mole 7-medG per mole dG and 0 .254 mu mole O-6-medG per mole dG with a 2-3 fold variation between in dividuals. No correlation was observed between the levels of the two a dducts suggesting inter-individual differences in formation and remova l of the two adducts. Failure of treatment was observed in five patien ts and this was not correlated with higher or lower levers of 7-medG o r O-6-medG. Other adducts formed as a consequence of treatment with PC Z or other MOPP/ABV components could have more relevance in this respe ct. The ability to measure DNA methylation adducts at the individual l evel following exposure to PCZ or other methylating chemotherapeutic d rugs (e.g. dacarbazine) could be useful in prospective studies of seco ndary cancer in Hodgkin's disease patients.