Effect of 1,3- Bis -(2-Chloroethyl)-1-Nitrosourea on Saccharomyces cerevisiae. ∗

Abstract

Summary

The pharmacological actions of 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) were investigated with a microbial test system. The antimicrobial spectrum of BCNU differed from that of the parent 1-methylnitrosourea (MNU) and that of nitrogen mustard (HN2). Computer analysis likewise showed certain differences in the dose-response relationships of S. cerevisiae to each of the 3 drugs; HN2 and BCNU yielded similar numerical slopes and LD₅₀ values but the form of the curve at times differed between the 2 drugs. With MNU, much lower slopes and higher LD₅₀ values were obtained. The inhibitory action of BCNU on yeast was antagonized by cysteine and by dithiothreitol (DTT); only cysteine annulled the action of HN2. Neither sulfhydryl compound antagonized the inhibitory action of MNU. BCNU was apparently more stable in solution than HN2. In the presence of viable yeast cells, there was a slow decrease in concentration of BCNU in the supernatant solution. This decrease was much less in the presence of nonviable cells. Glycolysis in yeast was limited by BCNU and this was not antagonized by nicotinamide or adenine. Addition of the drug to cultures of S. cerevisiae reduced the concentration of protein, DNA, insoluble RNA, and soluble RNA in the cells. These dose-response regression lines were almost parallel, but DNA was depressed to a somewhat greater extent than the others. Binding of BCNU to pyrimidines or purines could not be demonstrated.