Methylation in the phage carried by Escherichia coli 15T − (DNA methylation in phage ψ)

Abstract

Mitomycin C (MMC), actinomycins (ACMs), daunomycin (DNM) and adriamycin (ADR) are antineoplastic, antibiotics, with the anthracyclines (DNM and ADR) being more promising that the others. All these chemicals interact with DNA. MMC brings about cross-linking of the DNA strands and acts as mono-, as well as, bifunctional alkylating agent. The other three intercalate with the DNA molecule. ACMs, especially ACM-D, inhibits RNA synthesis preferentially and discriminates between different species of RNA. At high concentrations, DNA, RNA and protein synthesis are all inhibited by any of these antibiotics. The agents effect the cell cycle traverse at various stages; MMC being most unspecific of all. Mitotic cells at post-G2 stages are the least effected by any of these chemicals.All these chemicals induce chromosome aberrations of chromatid type. The anthracyclines, in addition, produce chromosome-type aberrations perhaps by affecting the single stranded G1 chromosome. Rejoining occurs, but MMC creates a high frequency of quadriradial configurations by utilizing the analogous nucleotide sequences in the repetitive DNA. At other points, it mostly creates free fragments. The mechanisms of action appear to be different for induction of chromosome aberrations by MMC, ACT and the anthracyclines. Both in vitro and in vivo aberration induction has been reported. The associated phenomenon of sister chromatid exchanges is strongly potentiated by these agents.MMC has been a known mutagen in both akaryotes and eukaryotes, and it also increases the frequency of meiotic recombination. ACM-D does not appear to strongly effect these phenomena while sufficient data with the anthracyclines are not available, and perhaps, will turn out to be generally negative. MMC and ACM-D also induced somatic recombination and somatic mosaicism; the former is a potent recombinogen. Correlation between genetic effect and the information available on the binding of ACM-D to chromatin is discussed and some space has been allocated to the discussion of resistance and cross resistance induced by the four chemicals.The data point to a strong need for testing of chemicals for genetic toxicology; particular attention must be given to the subject of co-mutagenicity.