Sacrosine- and prolinedithiocarbamate pretreatment increases the therapeutic efficacy of doxorubicin, methotrexate, teniposide, mitoxantrone or cyclohexylchloroethylnitrosourea in leukemia L1210.
The influence of different doses of the hydrophilic sarcosine- or prolinedithiocarbamate on the chemotherapeutic efficacy of doxorubicin, teniposide, methotrexate, mitoxantrone or cyclohexylchlorethylnitrosourea was evaluated in female B6D2F1 mice bearing leukemia L1210, implanted intraperitoneally. The simultaneous administration of these dithiocarbamates and the drugs used induced no increase of the therapeutic efficacy of the combinations compared to the corresponding dose of the drug and simultaneously applied saline. The results indicate that the subcutaneous pretreatment with sarcosine- or prolinedithiocarbamate increased the therapeutic efficacy of the drugs used compared to the corresponding monotherapy, in which saline was applied in the same interval as the dithiocarbamate and the antineoplastic agents. Sarcosine- or prolinedithiocarbamate applied alone did not influence leukemia L1210. The increase of the efficacy of the drugs used by sequential combination with sarcosine- or prolinedithiocarbamate seems to be influenced predominantly by diminishing the toxicity as well as by modulating the chemotherapeutic action.
Institute of Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg.
H
H
Osswald
N
N
Frank
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003545:Cysteine / Q000494:pharmacology; D004317:Doxorubicin / Q000627:therapeutic use; D004357:Drug Synergism; D005260:Female; D007939:Leukemia L1210 / Q000188:drug therapy*; D008130:Lomustine; D008727:Methotrexate / Q000627:therapeutic use; D051379:Mice; D008811:Mice, Inbred DBA; D008942:Mitoxantrone / Q000627:therapeutic use; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D012521:Sarcosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013713:Teniposide / Q000627:therapeutic use; D013859:Thiocarbamates / Q000494:pharmacology*
D000970:Antineoplastic Agents; D013859:Thiocarbamates; C066229:prolinedithiocarbamate; C055171:sarcosine dithiocarbamate; D008130:Lomustine; D004317:Doxorubicin; D013713:Teniposide; D011392:Proline; D008942:Mitoxantrone; D003545:Cysteine; D008727:Methotrexate; D012521:Sarcosine