Induced resistance to alkylating agent toxicity obtainable by pretreatment with combinations of trace elements.

Survival (monitored as colony-forming ability) of Chinese hamster Cd(r) 20F4 cells following exposure to the alkylating agent melphalan was enhanced by pretreating cells with combinations of the trace elements zinc, selenium, and copper. Cultures simultaneously pretreated with any two trace elements prior to exposure to melphalan exhibited survival values that were either equivalent to (Zn + Cu or Zn + Se) or somewhat greater than (Se + Cu) the sum of survivals obtained in cultures pretreated with singly administered elements. Simultaneous pretreatment with all three trace element inducers produced dramatic increases in survival level upon subsequent challenge with melphalan that ranged from 20-to 130-fold over the levels achieved in non-induced cultures.