Induction of chromosome breaks and sister chromatid exchanges in patients with Hodgkin's disease by two combination chemotherapy regimens of different leukemogenic potential.
The success of various combination chemotherapies in the treatment of cancer is compromised by their potential to cause secondary leukemia. Previous studies have suggested that the alkylating agents used in some regimens are the major etiological factor in these leukemias. In this study, we compared the abilities of two standard regimens used in the treatment of Hodgkin's disease to cause chromosome breaks and sister chromatid exchanges, the two most common types of chromosomal damage induced by alkylating agents. These regimens are MOPP [mechlorethamine-vincristine (Oncovin)-procarbazine-prednisone] and CVPP-ABDIC [cyclophosphamide-vinblastine-procarbazine-prednisone-doxorubicin (Adriamycin)-bleomycin-dacarbazine-1-(2-chloroethyl)-3-cyclohexyl-1- nitrosourea]. Our study demonstrated that (a) levels of spontaneous chromosome breaks and sister chromatid exchanges were low in untreated Hodgkin's disease patients; (b) significantly higher levels of these damages were induced in patients receiving eight cycles of CVPP-ABDIC, as compared with their pretreatment levels; (c) significantly elevated levels of sister chromatid exchanges, but not chromosome breaks, were induced in patients receiving two cycles of MOPP; and (d) no differences in the effect of these two regimens on cell cycle kinetics were observed. Although MOPP therapy has been reported to have higher rates of secondary leukemia than CVPP-ABDIC, our studies show that eight cycles of CVPP-ABDIC are more potent than two cycles of MOPP in inducing chromosome damage in patients during treatments.
Sen
P
P
Division of Laboratory Medicine, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Bailey
N M
NM
Hagemeister
F B
FB
Liang
J C
JC
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001761:Bleomycin / Q000009:adverse effects; D002453:Cell Cycle / Q000187:drug effects; D002875:Chromosomes / Q000187:drug effects; D004249:DNA Damage; D003606:Dacarbazine / Q000009:adverse effects; D004317:Doxorubicin / Q000009:adverse effects; D006689:Hodgkin Disease / Q000188:drug therapy*; D006801:Humans; D008130:Lomustine / Q000009:adverse effects; D008466:Mechlorethamine / Q000009:adverse effects; D009603:Nitroso Compounds / Q000009:adverse effects; D011241:Prednisone / Q000009:adverse effects; D011344:Procarbazine / Q000009:adverse effects; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D014747:Vinblastine / Q000009:adverse effects; D014750:Vincristine / Q000009:adverse effects
D009603:Nitroso Compounds; D001761:Bleomycin; D011344:Procarbazine; D008466:Mechlorethamine; D014750:Vincristine; D014747:Vinblastine; C041148:N-(2-chloroethyl)-N-nitrosoacetamide; D008130:Lomustine; D003606:Dacarbazine; D004317:Doxorubicin; D011241:Prednisone