Detection of DNA methylation adducts in Hodgkin's disease patients treated with procarbazine

Abstract

The aim of the present study was to assess the relationship between dose of the methylating agent procarbazine (PCZ), DNA methylation adduct formation andresponse to chemotherapy treatment in 23 Hodgkin's disease patients receiving MOPP/ABV combination therapy. The DNA adducts, 7-methyldeoxyguanosine (7-medG) and0⁶-methyldeoxyguanosine (0⁶-medG), were measured in leucocytes at the end of the first cycle of PCZ treatment (77–100 mg m^Z per day). 7-medG was detected in only two patients prior to treatment and0⁶-medG was below the detection limit (0.08 pole per mole dG) in all subjects prior to treatment. The mean levels after PCZ treatment were 12.55 pmole 7-medG per mole dG and0.254 μmole 0⁶-medG per mole dG with a 2–3 fold variation between individuals. No correlation was observed between the levels of the two adducts suggesting inter-individual differences in formation andremoval of the two adducts. Failure of treatment was observed in five patients andthis was not correlated with higher or lower levels of 7-medG or 0⁶-medG. Other adducts formed as a consequence of treatment with PCZ or other MOPP/ABV components could have more relevance in this respect. The ability to measure DNA methylation adducts at the individual level following exposure to PCZ or other methylating chemotherapeutic drugs (e.g. dacarbazine) could be useful in prospective studies of secondary cancer in Hodgkin's disease patients.

Key Words :

• DNA methylation adducts
• chemotherapy
• procarbazine
• molecular epidemiology
• Hodgkin's disease