SELECTIVITY OF ACTION OF ALKYLATING AGENTS AND DRUG RESISTANCE .I. BIOCHEMICAL CHANGES OCCURRING IN SENSITIVE AND RESISTANT STRAINS OF YOSHIDA ASCITES SARCOMA FOLLOWING CHEMOTHERAPY

A strain of the Yoshida ascites sarcoma which responded to chemotherapy with alkylating agents contained elevated levels of RNA, protein, glutamic acid and glycine, when compared with a drug-resistant strain. Curative treatment with individual alkylating agents resulted in the accumulation of DNA, RNA, protein and GSH in the sensitive cells. These reactions occurred during two time intervals: 0-24 hours and post-24 hours. Events occurring during the second period were broadly similar, irrespective of the identity of the drug used, while in the first period each drug elicited qualitatively and quantitatively different effects. In all cases the relative increase in glutathione content was greater than that of the other components measured. A reversible accumulation of glutathione, RNA and protein occurred in the sensitive cells following the administration, to the host rats, of therapeutically ineffective doses of a number of alkylating drugs. The time course of these changes differed according to the identity of the drug used, and provided a measure of the selectively different action of the latter on the cells. Similar effects were not observed in a resistant strain of cells. It is proposed that alkylating agents may have independent effects on several cellular constituents: DNA, RNA and protein; glutathione. © 1969, The British Empire Cancer Campaign for Research. All rights reserved.