Abstract
1) In order to clarify the mechanism of natural and acquired resistance of tumor cells to alkylating agents, comparative studies were made on cell permeability to methyl-bis(2-chloroethyl)amine N-oxide (MBAO) and methyl-bis(2-chloroethyl)amine (MBA), using the Yoshida ascites sarcoma, ascites hepatoma AH-130, AH-13, AH-602, AH-7974, and MBAO-resistant subline of AH-13.
2) On the basis of the known preferential affinity of alkylating agents to sulfhydryl groups, the permeability of tumor cells to alkylating agents was estimated by comparing the decrease of sulfhydryl content by contact with alkylating agents in intact tumor cells and in those whose cell membrane was previously destroyed. Sulfhydryl content was determined by the amperometric method.
3) Significant difference was not observed in the permeability to MBAO and MBA between the original AH-13 strain and its MBAO-resistant subline. The order of permeability in the original strains was the same in both MBAO and MBA. The order of decreasing permeability was AH-130, Yoshida ascites sarcoma, AH-13, AH-7974, and AH-602.
4) From the examination of cell permeability and that of sulfhydryl content reported in the previous paper, it was concluded that the non-protein sulfhydryl content and permeability of tumor cells play an important ròle in the mechanism of natural resistance of tumors to alkylating agents, while the development of acquired resistance to alkylating agents is chiefly due to an increase in non-protein sulfhydryl content.
5) It was further confirmed that the tumor cells which show a strong mutual adhesiveness are less permeable to alkylating agents.
