Abstract
Summary
The relationship between some of the chemotherapeutic effects of N-isopropyl-α-(2-methylhydrazino)-p-toluamide (MIH) and the development of resistance in Ehrlich ascites cells was explored. Whereas DNA and protein synthesis is moderately inhibited in these cells after the in vivo administration of the drug, the synthesis of RNA is stimulated. Cell division is markedly suppressed by MIH for periods of time beyond its effects on nucleic acid metabolism. Energy metabolism of the cells is not significantly affected by the drug. It is concluded that the primary chemotherapeutic effect of MIH is on some process associated with cell division other than nucleic acid or energy producing metabolism. A line of cells resistant to MIH was developed. Resistance was induced much more rapidly when MIH was given to coincide with periods of normal DNA synthesis. Resistance developed more slowly when the drug was given over a period in which DNA synthesis was depressed. In both cases, the resistant line was characterized by the appearance of two new metacentric chromosomes in each cell in mitosis.
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