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  • Title: Genetic effects of some new bifunctional and water-soluble analogs of the anti-cancer agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in Saccharomyces cerevisiae.
    Author: Siebert D, Eisenbrand G.
    Journal: Mutat Res; 1977 Jan; 42(1):45-50. PubMed ID: 321953.
    Abstract:
    A series of 1,1'-polymethylenebis-3-(2-chloroethyl)-3-nitrosoureas, 1-(omega-hydroxyalkyl)-3-(2-chloroethyl)-3-nitrosoureas, 1,1'(4-methyl-m-phenylenebis)-3-(2-chloroethyl)-3-nitrosourea, 2-[3-(2-chloroethyl)]-3-nitrosoureido-2-deoxy-D-glycopyranose (chlorozotocin and 1-(2-methanesulfonyloxyethyl)-3-(2-chloroethyl)-3-nitrosurea were examined for their genetic activities. BCNU was simultaneously tested as an established, clinically used reference compound. A diploid strain of Saccharomyces cerevisiae, heteroallelic at the gene loci ade2 and trp5, was used as a test system for the induction of mitotic gene conversion (intragenic recombination). All compounds showed strong genetic effects. In the series of aliphatic bifunctional nitrosoureas, 1,1'-ethylenebis-3-(2-chloroethyl)-3-nitrosourea (1) was the most active compound. The water-soluble derivatives, including chlorozotocin, displayed all genetic effects of the same order of magnitude. There was no correlation between genetic activity and chemotherapeutic potential of the test compounds.
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