Studies On The Effect OF Azaserine On DNA

Abstract

Azaserine (O-diazoacetyl-L-serine) is known to be a non-competitive inhibitor of two enzymes necessary for de novo purine biosynthesis. Work done in this laboratory and others, however, indicates that much of azaserine’s effect in cytotoxicity, mutagenesis and carcinogenesis can be attributed to its action on DNA. DNA repair-deficient strains of Escherichia coli are found to be more sensitive to azaserine cytotoxicity and, in cases, to azaserine mutagenesis than the wild type E. coli. Attempts at showing an in vitro effect of azaserine on DNA have not been conclusive as of yet. An interesting aspect of azaserine cytotoxicity is that it can be partially reversed by growth in low levels of the alkylating agent N-methyl-N'-nitro-N-nitroso-guanidine. This adaptive response suggests that part of the in vivo action of azaserine involves an alkylation of the DNA.