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Title: Attempted induction of resistance to melphalan by pretreating Chinese hamster cells with subtoxic doses of the drug

Technical Report ·
OSTI ID:6309445

By pretreating the line Chinese hamster (CHO) cells with multiple subtoxic doses of melphalan before challenge with a toxic dose, we established optimal conditions to increase the resistance of the cells to melphalan toxicity. Variables examined included: (1) level of drug used to induce protection (0.0008 to 0.8 ..mu..M); (2) interval between administration of successive low doses of drug (3 to 12 h); and (3) duration of induction period (24 to 96 h). The greatest degree of protection (an increase by 2 to 2.5 times in survival following challenge with 16 ..mu..M melphalan for 2 h) was achieved with a level of 0.08 ..mu..M melphalan administered every 6 h for 48 h. Combining the low-level drug induction protocol described above with our previously described trace element induction protocol (treatment with 125 ..mu..M CuCl/sub 2/ for the last 9 h of the induction period) increased survival slightly over that achieved with either single-induction protocol. If we assume that the induction protocols yielded a slight but real degree of protection, it appears that the induced protection comprises a common component representing activities elicited by the two induction protocols and a component that represents protective processes that are unique to a given induction protocol. 10 references, 1 figure, 3 tables.

Research Organization:
Los Alamos National Lab., NM (USA)
DOE Contract Number:
W-7405-ENG-36
OSTI ID:
6309445
Report Number(s):
LA-10176-MS; ON: DE85002342
Resource Relation:
Other Information: Portions are illegible in microfiche products. Original copy available until stock is exhausted
Country of Publication:
United States
Language:
English