Induction Of SOS Functions Research Articles

Antitumor activity of platinum complexes.

Contemporary ideas about the mechanism of antitumor activity of platinum complexes are reviewed and discussed. The induction of SOS functions in bacteria is emphasized and an analogous mechanism in animal cells is suggested. The fate of the leaving ligand in the body is not known. Therefore the complex which reaches the target DNA may be very different from the applied compound. Even the amino ligand may be detached in the body, probably as part of the detoxication by binding to proteins. In the case of fast or medium-speed reactive complexes most of the platinum is inactivated by binding to proteins, whereas slow-reacting drugs are mostly excreted unchanged in the urine. Thus, the quantity of the complex which reaches the target is also difficult to assess. Due to peculiar pharmacokinetics, the results obtained with poorly soluble compounds administered in the solid form cannot be compared with those obtained in true solutions. There are many reasons for believing that the study of a coordination anticancer drug may contribute to our understanding of cancer growth and its reversal.

Molecular Mechanism for the Induction of “SOS” Functions

This chapter describes the characterization of the early molecular events that lead to the induction of prophages and SOS functions. The chapter also obtains preliminary evidence that specific oligodeoxynucleotide, such as d(A-G-G), inactivate phage (φ80 and λ) repressors in the permeabilized cells. This strongly suggests that specific oligodeoxynucleotide or single-stranded DNAs with specific base sequences are involved in the induction of SOS functions. Permeabilized and biologically active E.coli cells were obtained by plasmolysis and incubation of the cells in a reaction mixture that allows protein synthesis. These cells become permeable to low-molecular-weight proteins and oligodeoxynucleotide. Using this system, one studied two types of prophage induction. One is the induction by low-molecular-weight DNAse, such as micrococcal and pancreatic DNase, and the other by specific guanine-containing oligodeoxynucleotide. Prophage induction by the DNAse was dependent on a functional recBC-DNase and degradation of the DNA by the enzymes. On the other hand, the oligodeoxynucleotide induction was independent of recBC-DNase and did not require degradation of chromosomal DNA. There are two classes of guanine-containing deoxy oligonucleotides that are effective in prophage induction. One is specific deoxydinucleotides having the sequence A(or G or 1)-G; the other is oligodeoxyguanylates with a 5’ phosphate and a chain length between 6 to 18.

Survival and mutagenesis in UV-irradiated phage: multi-hit kinetics of mutation induction and lack of indirect induction by infection with UV-irradiated phage of error-prone repair.

The paper is concerned with the question of whether WEIGLE-reactivation (WR) and WEIGLE-mutagenesis (WM) can be indirectly induced by infection with UV-irradiated phage. Experiments neither with phage lambda of Escherichia coli nor with phage chi of Serratia marcescens show such induction-In this respects phage DNA differs from F'-DNA or Hfr-DNA; possible explanations are discussed. In both systems clear phage mutations can also be induced by UV without irradiation of the host cells; they appear, in unirradiated and irradiated host cells, with an increase of frequency which is greater than proportional to the UV dose. It is concluded that mutation induction of phage in the unirradiated host cells is due to a low level constitutive mutagenic repair; this could either be due to "spontaneous" induction of the mutagenic SOS-function or it could be a mechanism different from this one. Host irradiation would give rise to additional activity by the induced SOS-function leading to WR and WM. It is further concluded that deviation of the induction kinetics from a linear dose-dependence is not due to the necessary induction of SOS-functions.

Molecular Events and Molecules That Lead to Induction of Prophage and SOS Functions

Inhibition of DNA replication in bacteria induces a variety of cellular processes which have been designated as SOS functions (Witkin 1974; Radman 1974). A typical example of the SOS functions is prophage induction which was originally discovered by Lwoff in Bacillus megatherium following ultraviolet (UV) irradiation (Lwoff et al. 1950). Certain genes and their products have now been identified with the induction of SOS functions (for review, see Witkin 1976). Among them, the X protein associated with induction of SOS functions (Gudas and Pardee 1975) and the recA-gene protein product (McEntee et al. 1976) were recently demonstrated to be identical (Emmerson and West 1977; McEntee 1977; Gudas and Mount 1977). There is evidence that protease activity associated with recA protein inactivates repressor molecules (Roberts et al. 1977). Little is known, however, about the initial molecular events which trigger the SOS functions. Kirby et al. (1967) proposed that an adenine derivative...