Toxicity of aziridinylbenzoquinone for aerobic and hypoxic cells of a transplanted mouse mammary tumor and interaction of the drug with radiation and adriamycin.
Aziridinylbenzoquinone (AZQ), an experimental drug with good tissue penetration, was tested against aerobic and hypoxic cells of the 16/C transplantable mouse mammary tumor. The drug was given alone or with local tumor radiation to kill most of the aerobic cells. The end point of response was growth delay. AZQ gave additive effects with tumor irradiation and was equally effective against aerobic and hypoxic cells. AZQ was also given in combination with Adriamycin, since the latter drug is known to have poor penetration in solid tissue. Combined treatment led to greater antitumor effects than were obtained with maximally tolerated doses of either drug alone. Isobologram analysis of the interaction between the drugs suggested a superadditive effect, and the addition of Adriamycin had little effect on myelosuppression induced by AZQ. The combination of AZQ and Adriamycin is worthy of further study.
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001388:Aziridines / Q000627:therapeutic use* / Q000633:toxicity; D001389:Azirines / Q000627:therapeutic use*; D016227:Benzoquinones; D002455:Cell Division / Q000187:drug effects; D053138:Cyclohexenes; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D007958:Leukocyte Count; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D051379:Mice; D009368:Neoplasm Transplantation; D010100:Oxygen
D000970:Antineoplastic Agents; D001388:Aziridines; D001389:Azirines; D016227:Benzoquinones; D053138:Cyclohexenes; C006052:2,5-bis(1-aziridinyl)-3,6-bis(2-methoxyethoxy)-4-benzoquinone; D004317:Doxorubicin; D010100:Oxygen