[Study on the toxicity and antitumor activity of adriamycin-DNA and amsacrine-DNA complexes in mice].
We have compared in vitro binding of adriamycin (ADR) and amsacrine (AMSA) with DNA, the toxicity, and the antitumor activity of ADR-DNA and AMSA-DNA, after intraperitoneal (ip) injection in mice. The binding of ADR with DNA is 100-fold higher than that of AMSA with DNA. The overall toxicity of ADR-DNA is significantly lower than that of ADR. ADR-DNA is more effective than ADR against three models of S180 sarcoma (by sc, ip and i.v. inoculation into mice). The peak levels of ADR-DNA and ADR were 265 +/- 24 ng.ml-1 versus 108 +/- 16 ng.ml-1 (P < 0.01). AUC 0-12 h were 1064 +/- 84 ng.h-1 x ml-1 versus 382 +/- 27 ng.h-1 x ml-1 (P < 0.01). The levels of ADR in most of tissues and tumor after administration of ADR-DNA were higher than those after administration of ADR. Moreover, there is no difference in toxicity, therapeutic effects as well as AUC between AMSA-DNA and AMSA.
Zhang
X G
XG
Department of Clinical Pharmacology, North Taiping Road Hospital, Beijing.
Wu
D Z
DZ
D000677:Amsacrine / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity*; D000818:Animals; D004247:DNA / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity*; D018736:DNA Adducts; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity*; D004337:Drug Carriers; D005260:Female; D007928:Lethal Dose 50; D051379:Mice; D009368:Neoplasm Transplantation; D012510:Sarcoma 180 / Q000188:drug therapy / Q000378:metabolism; D014018:Tissue Distribution
D018736:DNA Adducts; D004337:Drug Carriers; C080713:amsacrine-DNA; C031902:doxorubicin-DNA; D000677:Amsacrine; D004317:Doxorubicin; D004247:DNA