Interaction of radiation, dihydroxyanthraquinone, and adriamycin on the induction of acute lethality in mice

Abstract

The acute lethality induced by combinations of radiation, Dihydroxyanthraquinone (DHAQ), and Adriamycin (ADR) was investigated in mice. Whole-body irradiation produced acute lethality, with an LD- 50 30 of approximately 6.5 Gy. ADR and DHAQ produced LD- 50 30 's of 14 and 4 mg/kg, respectively. When 10 mg/kg doses were fractionated into 5 × 2 mg/kg daily doses, both drugs were equally or more efficient at producing mortality, 90% by day 30. When 4 Gy radiation was combined with 5 mg/kg ADR or 5 mg/kg DHAQ, a response no greater than that produced by drug alone was obtained. However, when 5 mg/kg ADR was administered concomitantly with 5 mg/kg DHAQ, there was a less-than-additive induction of lethality, resulting in only 21% mortality by day 30. Since this response is similar to that seen after ADR only, it would appear that the DHAQ-induced toxicity was protected against. Less-than-additive effects were also observed for combinations of 5 mg/kg ADR with either 2.5 or 10 mg/kg DHAQ; and combinations of 10 mg/kg ADR with either 2.5 or 5 mg/kg DHAQ. If ADR and DHAQ (at doses of 5 mg/kg) were combined but with a 1 day interval between drugs, the protective effect was lost and animals died earlier than after either agent alone. At present, no definite explanation is available for this unusual protective effect of ADR against acute lethality induced by DHAQ.