Attempted use of zinc in vivo to protect against nitrogen mustard toxicity in tumor-free and in L1210 leukemia-bearing female B6D2F1 mice.
The use of alkylating agents in treating cancer is limited by their toxicity to both normal and tumor tissue. Early in vitro studies indicated that zinc might be effective in mitigating this toxicity to normal tissue. The present studies were done to determine the capability of zinc to induce in vivo a protective response to an alkylating agent without also contributing to mortality. Tumor-free and L1210 leukemia-bearing female B6D2F1 mice were treated with zinc before administration of the alkylating agent nitrogen mustard. Protocols for administration route and frequency as well as the chemical formulation of the zinc were varied. The effect of a phytate-free diet was studied. Two parameters were used to determine the effectiveness of zinc in protecting animals from the toxicity of nitrogen mustard: the number of tumor-free mice that survived and an increase in the median life span of the tumor-bearing mice. The zinc-induction protocols used in these studies provided a limited degree of protection against nitrogen mustard toxicity in tumor-free female mice, but in tumor-bearing animals the protective response elicited with the protocols examined did not provide an appreciable therapeutic benefit.
Shackelford
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ME
Life Sciences Division (MS M880), Los Alamos National Laboratory, NM 87545.
Tobey
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RA
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000401:mortality; D051379:Mice; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D009588:Nitrogen Mustard Compounds / Q000037:antagonists & inhibitors*; D012016:Reference Values; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D015032:Zinc / Q000494:pharmacology / Q000627:therapeutic use*
D009588:Nitrogen Mustard Compounds; D015032:Zinc